Oxaliplatin (OXA), belongs to the class of platinum-based antitumor drugs. Among the standard chemotherapeutic agents, OXA succeeded in the treatment of different tumors. However, using of OXA prior or during pregnancy constitutes health challenge to mothers and their offspring owing to cumulative outcome. Propolis (PRO) is a resinous product collected by the bee "Apis mellifera" from plants to cement the beehives, and has a protective efficiency against many medication-toxicity. The present study aimed to appreciate the protective effect of PRO against OXA-induced toxicity on the mothers and their neonates. Thirty-five adult female Sprague-Dawley rats were equally divided into seven groups: the control pregnant group received distilled water; however, the groups 2, 3, and 4 received PRO (200 mg/kg body weight, orally/daily), OXA (3 mg/kg body weight, intravenous injection, three times/week), OXA+PRO, respectively, for 21 days pre-pregnancy; while, the groups 5, 6, and 7 received the same treatments and doses for 21 days during pregnancy. The results of the current study showed that – as compared to the OXA-induced renal and splenic toxicity in maternal rats and their neonates – co-administration of PRO with OXA either prior or during pregnancy conferred a crucial protective role to overwhelm the OXA-induced histopathological alterations in the renal and spleen tissues.