The research was implemented to assess the safety of feeding excess of pyrroloquinoline quinone disodium (PQQ·Na2) to 108 Duroc × Landrace × Large White weaned pigs (BW = 8.38 ± 0.47 kg). Pigs were weaned at 28 d and randomly distributed to one of three diets with six replicates and six pigs per replicate (three males and three females). Pigs in the control group were fed a corn-soybean meal-based diet (without growth promoter) while the two experimental diets were supplied with 7.5 and 75.0 mg/kg PQQ·Na2, respectively. Average daily gain (ADG), average daily feed intake (ADFI), feed conversion (F:G), diarrhea incidence, hematology, serum biochemistry, organ index and general health were determined. Diets supplementation with 7.5 mg/kg PQQ·Na2 in weaned pigs could increase ADG during the entire experimental period (p < 0.05). And there was a tendency to decrease F:G (p = 0.063). The F:G of weaned pigs fed 7.5 and 75.0 mg/kg PQQ·Na2 supplemented diets was decreased by 9.83% and 8.67%, respectively, compared to the control group. Moreover, pigs had reduced diarrhea incidence (p < 0.01) when supplemented with PQQ·Na2. No differences were observed between pigs supplemented with 0.0, 7.5 and 75.0 mg/kg PQQ·Na2 diets on hematological and serum biochemical parameters as well as histological assessment of heart, liver, spleen, lung and kidney. At day 14, pigs had increased activity of glutathione peroxidase (GSH-Px) (p < 0.05), catalase (CAT) (p < 0.05) and total antioxidant capacity (T-AOC) (p < 0.05), and the serum concentration of malondialdehyde (MDA) was decreased (p < 0.01) with PQQ·Na2 supplementation. At day 28, pigs had increased activities of total superoxide dismutase (T-SOD) (p < 0.01), GSH-Px (p < 0.01), CAT (p < 0.05) and T-AOC (p < 0.01), and serum concentration of MDA was lower (p < 0.01) with PQQ·Na2 supplementation. In conclusion, PQQ·Na2 can improve weaned pigs growth performance and serum antioxidant status. Meanwhile high PQQ·Na2 inclusion of 75.0 mg/kg does not appear to result in harmful effects on growth performance of pigs.