This study aimed to evaluate the potential protective role of encapsulated thyme oil (ETO) against zinc oxide nanoparticles (ZnO-NPs). ETO was prepared using a mixture of whey protein isolate, maltodextrin, and gum Arabic, and ZnO-NPs were synthesized using parsley extract. Six groups of male Sprague-Dawley rats were treated orally for 21 days included the control group, ZnO-NPs-treated group (25 mg/kg b.w), ETO-treated groups at low or high dose (50, 100 mg/kg b.w) and the groups received ZnO-NPs plus ETO at the two doses. Blood and tissue samples were collected for different assays. The results showed that carvarcol and thymol were the major components in ETO among 13 compounds isolated by GC-MS. ZnO-NPs were spherical and ETOs were round in shape with an average size of 38 and 311.8 nm, respectively. Administration of ZnO-NPs induced oxidative stress, DNA damage, biochemical, ctyogentical, and histological changes in rats. ETO at the tested doses alleviated these disturbances and showed protective effects against the hazards of ZnO-NPs. It could be concluded that encapsulation of thyme oil using whey protein isolate, maltodextrin and gum Arabic improved ETO properties, probably possess synergistic effects, and can be used as a promising tool in pharmaceutical and food applications.