As nano-zinc oxide (Nano-ZnO), a new type of nanomaterial, has antioxidant and intestinal protection effects, we hypothesized that dietary Nano-ZnO could modulate poor meat quality, oxidative stress and disturbed gut microbiota in the finishing pig model of naturally occurring intrauterine growth retardation (IUGR). A total of 6 normal-born weight (NBW) and 12 IUGR piglets were selected based on birth weight. The pigs in the NBW group received a basal diet, and IUGR pigs were randomly divided into two groups and treated with basal diet and 600 mg/kg Nano-ZnO-supplemented diet. Dietary Nano-ZnO ameliorated IUGR-associated declined meat quality by lowering the drip loss48h, cooking loss, shearing force andMyHc IIxmRNA expression, and raising the redness (a*), peak area ratio of immobilized water (P22), sarcomere length andMyHc IamRNA expression. Nano-ZnO activated the nuclear factor erythroid 2-related factor 2-glutamyl cysteine ligase (Nrf2-GCL) signaling pathway by promoting the nuclear translocation of Nrf2, increasing the GCL activities, and mRNA and protein expression of its catalytic/modify subunit (GCLC/GCLM), thereby attenuating the IUGR-associated muscle oxidative injury. Additionally, the composition of IUGR pigs’ cecal microbiota was altered by Nano-ZnO, as seen by changes in Shannon and Simpson indexes, the enhancedUCG-005,hoa5-07d05 gut groupandRikenellaceae RC9 gut groupabundance. TheUCG-005andhoa5-07d05 gut groupabundance were correlated with indicators that reflected the meat quality traits and antioxidant properties. In conclusion, Nano-ZnO improved the IUGR-impaired meat quality by altering water holding capacity, water distribution and the ultrastructure of muscle, activating the Nrf2-GCL signaling pathway to alleviate oxidative status and regulating the cecal microbial composition.