Aims: This study assessed the prophylactic or therapeutic effects of taurine (TR) and/or hesperidin (HES) on carbon tetrachloride (CCl4) induced acute kidney and testicular injury in rats. Main methods: Rats were randomly divided into nine experimental groups including control; corn oil; CCl4; HES/CCl4; TR/CCl4; HES + TR/CCl4; CCl4/HES; CCl4/TR; and CCl4/HES + TR groups. CCl4 was intraperitoneally injected with a single dose of 2 ml /kg b.w. HES and TR were orally gavaged twice weekly 100 mg/kg b.w. for four weeks. Kidney function, inflammatory response, sexual hormones, and oxidative stress indicators were assessed. Histomorphological and immune-histochemical studies of the inflammatory marker nuclear factor kappa (NF-κB) in renal and testicular tissues were performed. Key findings: The results showed that the TR and/or HES treatment significantly suppressed CCl4 induced rise of urea, uric acid, potassium, and follicle-stimulating hormone levels. However, significant restoration of sodium, testosterone, and luteinizing hormone was apparent in CCl4 exposed rats received HES and/or TR. Also, the HES and/or TR treatment significantly rescues CCl4 induced oxidative stress and inflammation. Moreover, the HES and/or TR dosing significantly repaired the CCl4 evoked altered renal and testicular architecture and suppressed NF-κB immunoexpression. Notably, alleviating CCl4 induced renal and testicular damage was more effective in the prophylactic groups than the therapeutic groups. Also, most of the estimated parameters of the HES + TR group did not significantly vary from those of single TR or HES. Significance: In conclusion, HES or TR could efficiently guard against CCl4 nephro-and reprotoxic effects, but both bioactive combinations afford only a limited synergistic outcome.