The current study investigated the radioprotective effect of Ocimum sanctum on the salivary gland of rats administered radioiodine (¹³¹I) and compared its efficacy with a known radioprotectant, amifostine. The experimental rats were divided in four groups and sacrificed in three different batches at 1, 3, and 6 months of time interval after 18.5 MBq/100g (i.p.) ¹³¹I exposure. Six months duration batch received ¹³¹I exposure twice with the gap of 3 months. Two groups of experimental rats were presupplemented with O. sanctum (40mg/kg for 5 days, orally) and amifostine (200 mg/kg, s.c) before ¹³¹I exposure separately. Increased Technetium-99m-pertechnetate (^99mTcO₄^- ) uptake at 30 minutes post injection in salivary glands of only ¹³¹I exposed rats may imply delay in clearance at 6 months of exposure in comparison to their counterparts sacrificed at 1 month. Parotid gland histology showed atrophy with lipomatosis in only ¹³¹I exposed rats at 3 and 6 months of duration. O. sanctum and amifostine presupplemented and subsequently exposed to ¹³¹I rats at 3 and 6 months duration exhibited comparable histopathology with controls. Our study indicates possible radioprotective effect of O. sanctum and amifostine against high-dose ¹³¹I exposure.