The objective of this study was to evaluate the effects of low protein diets added with protease on growth performance, nutrient digestibility, and blood profiles of weaned piglets and growing-finishing pigs. A total of 96 weaned pigs ([Yorkshire × Landrace] × Duroc) with average body weight (BW) of 6.99 ± 0.21 kg were used in a 20-week experiment. The dietary treatments were arranged in a 2 × 3 factorial design. Treatments were as follows: In phase 1 (1-2 weeks), two protein levels as high protein (HP; 19.0%), low protein (LP; 17.0%), and three protease (PT) levels (PT0, 0%; PT1, 0.3%; and PT2, 0.5%); in phase 2 (3-4 weeks), protein levels (HP, 18.05%; LP, 16.15%) and protease levels (0%, 0.3%, and 0.5%); in phase 3 (5-12 weeks), protein levels (HP, 17.1%; LP, 15.3%) and protease level (0%, 0.15%, and 0.3%); in phase 4 (13-20 weeks), protein levels (HP, 16.15%; LP, 14.45%) and protease level (0%, 0.15%, and 0.3%). At 4 weeks and 20 weeks after treatment, BW was higher (p < 0.050) in the PT2 group than PT0 group. From weeks 0 to 4, average daily gain (ADG) and feed efficiency (G/F) were higher (p = 0.006 and p = 0.014; p = 0.014 and p = 0.044, respectively) in the PT2 group than PT0 and PT1 groups. From weeks 16 to 20, ADG and G/F were higher (p < 0.001 and p = 0.009; p = 0.004 and p = 0.033, respectively) in the PT2 group than PT0 and PT1 groups. Crude protein (CP) digestibility was higher (p = 0.013, p = 0.014, and p = 0.035, respectively) in the low protein (LP) group than high protein (HP) group at weeks 4, 12, and 20. At weeks 4 and 20, the LP diet group had lower (p < 0.001 and p = 0.001, respectively) blood urea nitrogen (BUN) levels than the HP diet group. Therefore, a low CP diet added with protease could increase growth performance and CP digestibility of weaned piglets and growing-finishing pigs.