Exposure to xenoestrogens like 4-nonylphenol (NP) is recognized by disrupting endocrine functions and causes reproductive dysfunction in male fish. The present study aimed at investigating the 4-nonylphenol propensity to induce oxidative stress and hormonal disturbances in male catfish and at studying the protective role of quince (Cydonia oblonga). To fulfill this aim, catfish Clarias gariepinus were exposed to pure 100 μg/L 4-NP and to quince the leaf extract added to 4-NP, both for 15 days. The 4-NP exposure induced a marked increase in 17ß-estradiol (E2), LH, and cortisol, while thyroid hormone (TSH, T3), testosterone (T), and FSH levels noticeably decreased; however, 4-NP had no effect on T4 level. Moreover, 4-NP exposure was accompanied by histological impairments in testes. Existence of 4-NP was associated with oxidative damage as evidenced by the significant increase (p < 0.05) of the enzymes, superoxidase dismutase (SOD), catalase (CAT), acetylcholinesterase (AchE), glutathione s-transferase, total antioxidant capacity (TAC), and malondialdehyde (MDA). Adding quince was effective to neutralize hormonal levels and to repair the testicular histological alterations. In response to quince remedy, the enzymes AchE and MDA reduced significantly (p < 0.05), while limited or no response was detected for other tested enzymes. Our results concluded that quince can antagonize 4-NP toxicity in catfish, confirming that quince leaf extract displayed antioxidant activities against the toxicity of hazardous chemicals.