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ABSTRACT This study aimed to investigate the effect of Artemisia apiacea Hance supplementation on growth performance, cecal opportunistic bacteria, and antimicrobial defense using 120 rabbits. There were four experimental diets containing a control and A. apiacea Hance added at doses of 25, 50, and 75 g kg−1 of feed. The trial lasted for 70 days. The results showed that diets supplemented with A. apiacea Hance improved feed intake, body weight gain, and feed efficiency. Linear and quadratic responses were found between feed intake and herbal meal doses. For cecal opportunistic pathogenic bacteria, compared with the control treatment, the herb decreased cecal C. perfringens, Gram-negative bacteria, and Salmonella spp. by 9.5 to 56.8%. Linear responses of herb doses were found on the four bacteria and a quadratic response on Salmonella spp. In addition, the herb increased the mRNA levels by 12.6 to 57.8% of cecal defensive peptides, including neutrophil peptide defensing-3a, regenerating family member-3 gamma defensin beta-1, and galectin-4. These genes linearly responded to the herb doses. The obtained data suggest that A. apiacea Hance is effective to improve animal growth by beneficially regulating gut opportunistic bacteria and microbicidal peptide activity.