Cyclosporine A (CsA) is a drug used in autoimmune disorders and organ transplantations. Omega 3 fatty acids (O-3) and sesame oil (SO) have antioxidant properties. We aimed to investigate and compare the protective effects of O-3 and SO against CsA-induced nephrotoxicity. Seven groups of male Wistar albino rats were included in the study. In group 1 (control), saline was administered, and in group 2, CsA (subcutaneously) was administered. In group 3, CsA+SO (orally; p.o.) was given; in group 4, CsA+O-3 (p.o.) was given; and in group 5, CsA+SO+O-3 was given. In group 6, SO was administered, and in group 7, O-3 was administered. After 15 days of treatment, kidneys were excised. Histopathological evaluation, apoptotic cell count, and renal/hepatic function tests were performed. In group 2, vacuolar degeneration and necrosis of tubular cells as well as hemorrhagic foci were observed; the apoptotic cell number was higher than in the control (P < 0.001). In groups 3, 4, and 5, tubular scores and apoptotic cell count were lower than in group 2 (P < 0.01 and P < 0.001, respectively). In groups 6 and 7, healthy renal histology and a few apoptotic cells were determined. In groups 2, 3, 4, and 5, blood urea nitrogen was higher and albumin was lower than in the control (P < 0.001). Liver enzymes were unchanged. O-3/SO showed similar protective effects against CsA-induced nephrotoxicity, as revealed by a remarkable decrease in histopathological changes and apoptotic cell count. However, impaired renal function tests were not improved with O-3/SO treatment. SO and O-3 can be used as chemoprotectants against CsA.