Cyanide is among the ubiquitous chemicals that humans are usually exposed to and it is well documented that cyanide induces infertility in humans and experimental rodents. However, the pathogenesis remains unknown. Likewise, quercetin is an important nutraceutical that detoxifies reactive oxygen species, but its effects on testicular damage is not clear. The present study investigated the role of nutraceutical, quercetin on cyanide-induced testicular toxicity and probable involvement of cAMP-response-element modulator (CREM) which is a transcription factor necessary for the process of spermatogenesis. Thus, this work hypothesized that quercetin will mitigate endocrine dysfunction induced by cyanide. Seventy-two adult male Wistar rats were divided into seven groups (A to G). Groups A, B, C, F and G comprised of eight (8) rats per group while groups D and E comprised of sixteen (16) rats per group. Group A was designated as control while Groups B and C were given 0.5 and 1 mg/kg of cyanide respectively for 56 days. Group D and E received 0.5 and 1 mg/kg body weight cyanide respectively for 30 days. At day 30, eight animals were sacrificed from Group D and E and the remaining eight (8) rats were subdivided into sub-groups (D1 and E1) and were given 20 and 40 mg/kg of quercetin respectively for twenty-six (26) days. Group F and G were given concurrent administration of cyanide and quercetin at a dose of 0.5 + 20 mg/kg and 1 + 40 mg/kg respectively for 56 days. Body and testicular weight were significantly reduced in cyanide treated groups while quercetin modulates the reduction. Significant down-regulation of CREM gene and reduction in serum level of follicle stimulating hormone (FSH), Luteinizing hormone (LH), testosterone, glutathione peroxidase (GPx) and zinc in cyanide-treated groups, whereas administration of quercetin concomitantly with cyanide exposure or post-treated significantly reversed the alterations.