Background <p>Testicular dysfunction is the potential side effects of cisplatin. This investigation aimed to assess the efficacy of hesperidin and rutin on cisplatin-induced testicular dysfunction in rats. Forty adult male rats were divided into: Group (1): control; Group hesperidin (2): Rats were given 50&#xa0;mg hesperidin; Group rutin (3): Rats were given 75&#xa0;mg rutin; Group hesperidin/rutin (4): Rats were treated with both hesperidin and rutin; Group cisplatin (5): The animals were intraperitoneally received 7&#xa0;mg cisplatin at a single dose; Group cisplatin/hesperidin (6): Rats were received hesperidin after cisplatin injection; Group cisplatin/rutin (7): Rats were received rutin after cisplatin injection; and Group cisplatin/hesperidin/rutin (8): Rats were received both hesperidin and rutin after cisplatin injection.</p> Results <p>Cisplatin injection caused a remarkable decline in the epididymal total sperm count with a marked increment in tail malformed sperm and disorder in testes parameters associated with disturbance in serum hormonal profile and enzyme activities. This damage was pronounced in the histological studies in addition to the decrease in the B-cell leukemia/lymphoma 2 (Bcl-2) expression in the immunohistochemical investigation. The treated groups with hesperidin and/or rutin showed a significant amelioration effect in all studied parameters.</p> Conclusion <p>The treatment with hesperidin or/ and rutin encourages the clinical use of these compounds as a management for testicular failure and the combination of hesperidin and rutin enhance the therapeutic efficacy relative to the administration of either compound alone.</p>