The present study evaluated the effects of dietary medium-chain fatty acid (MCFA) and Bacillus on growth performance, nutrient digestibility, antioxidant capacity, colonic fermentation, and microbiota of weaning piglets. A total of 400 weaned piglets were randomly divided into 4 treatments, with 10 replicates per treatment and 10 pigs per replicate. The treatment included: basal diet (control, CON), basal diet with 0.588 g/kg MCFA (MCF), basal diet with 1.3 × 109 CFU/kg Bacillus (BAC), and basal diet with 0.588 g/kg MCFA and 1.3 × 109 CFU/kg Bacillus (SYN). Compared with CON group, the average daily gain of MCF and SYN in the early (1 to 9 d) and whole stage (1 to 36 d) of trail were improved (P < 0.05), the feed to gain ratio of MCF in later (10 to 36 d) and whole stage of trial were decreased (P < 0.05), and the diarrhea rate of SYN in the early stage (1 to 9 d) of trial decreased (P < 0.05). The digestibility of dry matter, ether extract, acid detergent fiber digestibility of MCF were decreased (P < 0.05) compared with CON. The serum d-lactic acid in MCF, BAC, and SYN were lower (P < 0.05) compared with CON group. Compared with CON group, the contents of total antioxidant capacity, superoxide dismutase, and glutathione peroxidase were greater (P < 0.05), whereas the content of malondialdehyde and the contents of colonic isobutyrate and isovalerate were lower (P < 0.05) in MCF. The microbial Shannon and Simpson diversity was lower in MCF (P < 0.05) than that in BAC and SYN. The relative abundance of Prevotella was greater (P < 0.05), whereas the Treponema and Oscillibacter were lower (P < 0.05) in MCF than that in BAC and SYN. In addition, the metabolic pathways of bacteria such as pentose phosphate pathway, adenosine nucleotides degradation II were enhanced (P < 0.05), whereas the pathways such as incomplete reductive TCA cycle, and TCA cycle IV (2-oxoglutarate decarboxylase) were decreased (P < 0.05) in MCF compared with BAC. The results indicated that dietary MCFA and Bacillus in combination improved the intestinal barrier function of piglets by changing the intestinal microbiota and its metabolic function, and finally alleviated the diarrhea rate in early weaning stage and improved growth performance in whole trial period. In addition, MCFA was effective in improving feed efficiency and antioxidant capacity of piglets.