ʎ-cyhalothrin (LCT) is pyrethroid insecticide that is used worldwide for pest control in agriculture and household use. Cleome droserifolia extract (CDE) is a potential antioxidant protecting cells from oxidative stress. Mesenchymal stem cells (MSCs) have the capacity to generate multiple distinct cell lineages. The present study investigates the protective and therapeutic effect of CDE and MSCs, separately on LCT-induced changes in male rats. Seventy adult male albino rats were divided into seven groups: group I: served as control; group II: received LCT i.p. only (6.2 mg/kg b.wt.); group III: received CDE only (100 mg/kg b.wt., p.o.) for eight weeks; group IV: received CDE as a protective agent daily for eight weeks, then followed by the administration of LCT (i.p.) three times a week for two weeks; group V: exposed to LCT (i.p.) three times a week for two weeks, then treated with the CDE daily for 8 weeks; group VI: rats injected (i.v.) with a single dose of MSCs (1x10⁶ cells/cm² saline), then received dose of LCT (i.p.) three times a week for two weeks and group VII: rats received dose of LCT (i.p.) three times a week for two weeks, then injected (i.v.) with a single dose of MSCs. Results showed that, LCT caused significant reduction in the body and testis weight, and markedly impaired sperm quality (a count, viability, motility and abnormality). Also, LCT elicited significant declines in serum testosterone, whereas, serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) were significantly increased. Compared to LCT-treated animals, CDE in the protective group markedly restored the alteration of body and testis weights, sperm indices and sexual hormones. However, CDE in the curative group was found to be less effective in restoring LCT induced morphological and biochemical alterations. Transplantation of MSCs as being a therapy after LCT intoxication showed significant improvement in the activity of all parameters rather than their protective effect which showed minimal protection against LCT. In conclusion, data of this study revealed that the protective by CDE and therapeutic by MSCs are more effective than therapeutic by CDE and protective by MSCs in ameliorating LCT-induced testicular damage and improvement of male fertility and reproductive functions.