The present study was designed to detect the active constituent of different plants including Capparis spinosa ,Rumex acetosella, Trifolium pratensa ,and Solanium nigrum. The cytogenetic effects of ethanolic extract of C.spinosa, methanolic extract of R.acetosella and methotrexate on laboratory mice (in vivo) and on human blood lymphocyte (in vitro), with the comparison between the cytotoxic effects of these two plants extracts with those of MTX and MMC drugs on the tumor and normal cell lines were studied.These investigations were performed under four successive profiles: A-profile One: Chemical investigation of C.spinosa ,R.acetosella,T.pratense and S.nigrum for different active class compounds are evaluated .The HPLC analysis was carried out for ethanolic extract of C.spinosa and methanolic extract of R.acetosella using the flavonoids standards (Rutin and Qurecetin) . The following results were obtained: 1- Chemical investigation shows that C.spinosa and R.acetosella contain different active compounds such as flavonoids and glycosides. 2- HPLC analysis showes that both C.spinosa and R.acetosella contain high level of rutin and qurecetin flavonoids. B-Profile Two : The effects of ethanolic extract of C.spinosa ,methanolic extract of R.acetosella and methotrexate on albino mice (in vivo) were evaluated by employing the following parameters: Mitotic index, chromosome aberration, micronucleus in bone marrow, the total and differential count of leukocyte, mitotic index in mouse testis, sperm head and tail morphology, in addition to serum level of liver function enzyme Glutamic Oxaloacetic Transaminase (GOT),Glutamic Pyruvic Transaminase(GPT) and specific activity of serum adenosine deaminase (ADA). The following results were obtained: 1- Methotrexate reveals clear effects in reducing mitotic index and increased chromosomal aberration in mouse bone marrow cells(in vivo) and caused an increase in the percentage of micronucleus . 2- Methotrexate caused a significant reduction in mitotic index of mouse testis and cause an induction in the abnormalities of sperm head and tail morphology. 3- Methotrexate reveals clear reduction in the total and differential counts of white blood cells by the reduction in lymphocytes, and neutophils.4-The specific activity of ADA was significantly decreased while GOT and GPT was significantly increased in animals treated with MTX. 5- Ethanolic extract of C.spinosa and methanolic extract of R.acetosella cause increased in mitotic index, and decrease the spontaneous frequency of chromosome aberration, and micronucleus in mouse bone marrow. 6- Both plants extracts caused a significant increase in mitotic index of mouse testis and decrease the abnormalities in sperms morphology. 7- Both plants extract increase the total and differential counts of white blood cells, through the increasing in the number of lymphocyte , monocyte and neutrophil. 8-The specific activity of ADA was significantly increased while the GOT and GPT were decreased in experimental animals treated with ethanolic extract of C.spinosa and methanolic extract of R.acetosella . C-Profile Three: The cytogenetic effects of ethanolic extract of C.spinosa, methanolic extract of R.acetosella and MTX drug on human blood lymphocytes (in vitro) were evaluated with further parameter: Blast index ,mitotic index , replicative index, chromosomal aberration, micronucleus and sister chromatid exchange. The following results were obtained: 1- Methotrexate reveals clear effects in reducing mitotic index in human blood lymphocytes(in vitro) ,and also caused reduction in Blast index, replicative index but an increases was observed in chromosomal aberration and sister chromatid exchange, and an increase in micronucleus in vitro. 2- C.spinosa and R.acetosella extract causes a significant increase in MI,BI,RI and both cause reduction in CA, MN, and SCEs in human blood lymphocyte in vitro. D-Profile Four: The cytotoxic activity of C.spinosa , R.acetosella extract, MTX and MMC drug on tumor cell lines were evaluated by using two tumor cell lines Human Epidermoid Larygocarcinoma(HEP-2) ,and Ahmed - Mohammed, Nahi mammary adenocarcinoma(AMN-3) ,and on normal cell line Rat embryo fibroblast (Ref). The following results were obtained: 1- Both MTX and MMC cause decrease in the number of cell viability of both tumor cell lines(HEP-2 and AMN-3) at high concentration of these drugs and both drugs have cytotoxic activity on normal cell line(Ref). 2- Both plants extract C.spinosa and R.acetosella indicated a clear cytotoxic activity with high significant in two tumor cell lines (HEP-2,AMN-3) and for all concentration . 3- These two plants C.spinosa and R.acetosella carried a compounds have less genotoxic effects than used anti cancer drugs MTX or MMC but they were very effective against tumor cells in vitro.