Cyclophosphamide (CP) is very well-known anticancer drug and commonly used against various cancers. CP therapy is related to female ovarian cancer and causes female infertility. The ovarian cancer associated with the increase oxidative stress and inflammatory reaction. Syringic acid (SA) is very well phyto-constituent and already proof antioxidant and anti-inflammatory effects on various diseases. We investigated the chemoprotective impact of SA on CP mediated ovarian damage, and the underlying mechanism. CP (75 mg/kg) was used to cause ovarian damage and rats were randomly divided into separate groups and received a different dose of SA for 14-day. Body weight, food and water intake were determined. Ovarian weight and tumor index was measured. Antioxidant parameters were determined in the serum and ovarian tissue. Pro-inflammatory cytokines, apoptosis parameters and inflammatory mediators were estimated in the serum. Hormonal parameters and Histomorphometry were estimated. Dose dependently treatment of SA significantly (p < 0.001) decreased the levels of biochemical parameter such as nitric oxide (NO), myeloperoxidase (MPO) and augmented the antioxidant parameters include catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and reduced malondialdehyde (MDA) level in serum and ovarian tissue. SA treatment significantly (p < 0.001) suppressed the level of luteinizing hormones (LH), anti-mullerian hormone (AMH), estradiol (E2) and folliclestimulating hormone (FSH) as well as ovarian follicles. SA significantly (p < 0.001) down-regulated cytokines, inflammatory mediator and caspase-3 parameters. Taken altogether, we conclude that SA considerably reduced ovarian damage via reduced oxidative stress and inflammatory reaction.