This study aimed to investigate the effects of diets with and without antibiotics supplementation and diets with 18.5 and 13.0% crude protein (CP) on growth performance, carcass characteristics, disease incidence, fecal microbiota, immune response, and antioxidant capacity of growing pigs. One hundred and eighty pigs (59-d-old; 18.5 ± 2.5 kg) were distributed in a randomized complete block design in a 2 × 2 factorial arrangement, nine replicates, and five pigs per pen. The factors were CP (18.5% or 13.0%) and antibiotics (none or 100 mg/kg tiamulin + 506 mg/kg oxytetracycline). Medicated diets were fed from d 59 to 73. After that, all pigs were fed their respective CP diets from 73 to 87 d. Data were analyzed using the Mixed procedure in SAS version 9.4. From d 59 to 73, pigs fed antibiotics diets had higher (P < 0.05) average daily feed intake (ADFI), average daily weight gain (ADG), gain to feed ratio (G:F), compared to the diets without antibiotics. From d 73 to 87 (post-medicated period), any previous supplementation of antibiotics did not affect pig growth performance. Overall (d 59 to 87), pigs fed antibiotics diets had higher (P < 0.05) G:F compared to pigs fed diets without antibiotics. In all periods evaluated, pigs fed 18.5% CP diets had higher (P < 0.05) ADG and G:F compared to pigs fed 13.0% CP. Pigs fed the 13.0% CP diets had lower (P < 0.05) fecal score and diarrhea incidence than those fed 18.5% CP. Pigs fed 18.5% CP diets had improved (P < 0.05) loin area compared to pigs fed diets with 13.0% CP. At 66 d of age, pigs fed antibiotics diets had lower (P < 0.05) alpha diversity estimated with Shannon and Simpson compared to the pig fed diets without antibiotics. At family level, pigs fed 18.5% CP diets had higher (P < 0.05) relative abundance of Streptococcaceae, and lower (P < 0.05) relative abundance of Clostridiaceae at d 66 and 87 compared with pigs fed 13.0% CP. Pigs fed antibiotics diets had lower (P < 0.05) immunoglobulin G and protein carbonyl concentrations at d 66 compared to the pigs fed diets without antibiotics. The reduction of dietary CP from 18.5% to 13.0% reduced the growth performance and loin muscle area of growing pigs, although it was effective to reduce diarrhea incidence. Antibiotics improved growth performance, lowered diarrhea incidence, improved components of the humoral immune response, and reduced microbiota diversity. However, in the post-medicated period, we found no residual effect on the general health of the animals, and considering the overall period, only G:F was improved by the use of antibiotics.