This study aimed to evaluate the supplementation of peppermint essential oil (Mentha piperita; PEO) in diets for juvenile Nile tilapia (Oreochromis niloticus). A feeding experiment with diets containing graded levels (0.0, 0.2, 0.4, 0.6, 0.8, and 1.0 g kg−1) of PEO was carried out with fish of 0.58 ± 0.08 g. The inclusion of graded levels of PEO in the diet improved the weight gain (0.52 g kg−1), feed intake (0.51 g kg−1), and feed conversion (0.51 g kg−1) of juvenile Nile tilapia in a quadratic pattern. Increasing levels of PEO also led to a linear decrease in body lipid content. The gut activity of the digestive enzymes amylase (0.54 g kg−1) and protease (0.39 g kg−1) increased quadratically, whereas lipase activity increased linearly. PEO increased the activity of the antioxidant enzymes catalase (CAT; 0.52 g kg−1) and superoxide dismutase (SOD; 0.58 g kg−1) while reducing the production of malonaldehyde (MDA; 0.40 g kg−1) and nitric oxide (NO; 0.63 g kg−1) in the liver. The results of this study provide evidence of the beneficial effects of PEO on the growth and health of Nile tilapia and recommend a dose of 0.6 g kg−1 as the optimal level of supplementation.