This experiment was conducted in weaned piglets to determine the effects of exogenous protease to low soybean meal (SBM) diets on growth performance, diarrhea rate, nutrient digestibility, and intestinal morphology. Seventy-two Duroc × Landrace × Yorkshire weaned barrows (21-day-old, 5.88 ± 0.95 kg) were randomly divided into four treatments with six replicates in each following a 2 × 2 factorial arrangement of SBM levels (0 to 14 d, 9%, 7.5%; 15 to 42 d, 20%, 18.5%) and protease (0 or 150 mg/kg) for a 42-day trial. Fecal samples were collected on days 11 to 14 and 38 to 42 of the experiment, and serum, intestinal tissue, and chyme samples were taken at the end of the experiments. Adding protease in low SBM diets had a significant increase in ADG (p < 0.05) and a decrease in F/G (p < 0.05). Protease significantly reduced the diarrhea rate (p < 0.05). Low SBM level decreased the apparent total tract digestibility (ATTD) of crude protein (CP) and ash (p < 0.05) but increased the ATTD of dry matter (DM), ash, organic matter (OM), and CP after the addition of protease (p < 0.05). The apparent ileal digestibility (AID) of aspartic acid (Asp), threonine (Thr), serine (Ser), alanine (Ala), lysine (Lys), and total amino acids (AAs) were significantly increased by protease supplementation (p < 0.05). Both the SBM-reduced and protease-added diets lead to lower albumin (ALB), albumin/globulin (A/G), and urea nitrogen (UREA) (p < 0.05), but greater globulin (GLOB) with low SBM diets (p < 0.05). The SBM-reduced and protease-added diets decreased the duodenum pH, respectively (p < 0.05). The protease increased the villus:crypt (V:C) in the duodenum and ileum, and ileal villus length (p < 0.05). In conclusion, the dietary supplementation of 150 mg/kg protease improved the intestinal health and performance of the weaned piglets and reversed the negative effect of a 1.5% SBM reduction in nutrient utilization, intestinal pH, and intestinal morphological parameters of weaned piglets.