Many side effects were detected for the use of cyclophosphamide as chemotherapeutic regimen for cancer patients among which are the increased oxidative stress and immune disturbance. The present study was designed to evaluate the effect of leaves of the two antioxidant-rich and commonly used edible plants namely; olive and guava against increased oxidative stress and disturbed immunity induced by cyclophosphamide (CP). Their methanolic and ethanolic extracts were subjected to analysis for the detection of their antioxidant activity by DPPH and their total and differential polyphenolic content by HPLC. A biological experiment was conducted comprising 6 groups of 6 rats in each, three groups of them were intraperitoneally injected with 40 mg/Kg B wt of CP for four successive days, one left as a positive control whereas the other two were given either olive leaves (OLs) or guava leaves (GLs) as 20% of their diet. The remaining three groups were injected by saline for four successive days, one was control negative group fed on basal diet while the other two were fed on either OLs or GLs as 20% of their diet. The experiment lasted for four weeks. Results revealed a relatively high antioxidant potency and polyphenolic content for OLs and GLs. Lymphocytopenia, neutropenia, thrombocytopenia, reduced monocytes and anemia were detected for the CP-injected group in addition to a reduction of reduced glutathione (GSH) and an elevation of the interleukin-6 (IL-6). Also, an alteration of the weight and histopathology of the thymus gland was recorded. All these aforementioned parameters were more or less restored to near their normal values of the control negative group in case of the two CP-injected groups that received either OLs or GLs reflecting their ameliorative impact against increased oxidative stress and disturbed immunity exerted by CP. Thus, it can be concluded that both OLs and GLs can be given as natural antioxidants to cancer patients during the period of cyclophosphamide chemotherapy to combat its concomitant increased oxidative stress and disturbed immunity.