Abstract Nanominerals are recently advocated for replacing their organic and inorganic counterparts. To examine their comparative efficacy, a study was designed to investigate the effect of supplementation of zinc through different sources and forms on apparent digestibility of nutrients, body weight gain, blood hemato-biochemistry, anti-oxidant activity, and serum mineral status in guinea pigs ( Cavia porcellus ). Groups (T 1 , control (inorganic zinc; ZnSO 4 ); T 2 , organic Zn (Zn methionine), commercial zinc nanoparticle (T 3 ), two zinc nanoparticles prepared in our laboratory (T 4 , T 5 ), were formed with six guinea pigs in each group (289 ± 3.5 g body weight) in a randomized block design. They were supplemented with 20 mg Zn per kg feed on dry matter basis for 90 days. At the end of the experiment, blood samples were collected from each animal through cardiac puncture and analyzed for hemato-biochemistry, oxidants/anti-oxidants, thyroid hormones and serum minerals. The results showed that intake and digestibility of nutrients were not affected by source of supplementation. Oxidants/anti-oxidants, thyroid hormones, hemato-biochemistry and serum minerals were also not affected by source of supplementation. However, the growth rate was higher (P = 0.031) in commercial nano-Zn supplemented groups (T 3 ) than in the other groups. Thus, supplementation of 20 ppm commercial Zn nanoparticles had a positive effect on growth rate of guinea pigs. But supplementation of Zn increased erythrocytic SOD activity and serum zinc level, irrespective of the source of Zn. As evidenced in our study spanning 90 days of trial, zinc nanoparticles can be safely supplemented up to 20 ppm level in the diet of guinea pigs.