Atopic dermatitis (AD) is a chronic inflammatory skin disease with an increasing global prevalence. Traditional intradermal acupuncture (IDA) offers continuous stimulation but may cause discomfort or allergic reactions due to the metal components. To address these limitations, a hyaluronic acid–based biodegradable microneedle acupuncture (BMA) device was developed, which provides therapeutic stimulation through biodegradable microneedles. This study aimed to evaluate the therapeutic efficacy and safety of BMA in adults with mild-to-moderate AD. Additionally, the impact of BMA on the gut microbiome was investigated. A total of 184 adults with mild-to-moderate AD were randomly assigned in a 1:1 ratio to either the BMA treatment group (n=92) or the sham control group (n=92). Treatments were administered three times per week for 4 weeks. The primary outcome was the change in the objective SCORing Atopic Dermatitis (O-SCORAD) index. Secondary outcomes included the Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), and pruritus Visual Analog Scale (VAS). Additional analyses included gut microbiome profiling via 16S rRNA sequencing, health economic evaluation, and safety assessments. At the 5-week assessment, the mean O-SCORAD score decreased by 12.57 ± 4.88 in the BMA group, compared to a decrease of 3.78 ± 3.74 in the control group, with a statistically significant between-group difference (p < 0.001). Secondary outcomes (EASI, DLQI, POEM, and VAS) also showed significantly greater improvements in the BMA group (all p < 0.05). According to the LEfSe analysis, Romboutsia was enriched in the sham control group after treatment compared with baseline. In contrast, the BMA group showed greater abundance of Lachnospiraceae uncultured at baseline, while Peptoniphilus became enriched after treatment. When comparing the gut microbiome between the post-treatment BMA and sham control groups, significant differences were observed in the relative abundance of Alistipes, Monoglobus, Prevotellaceae NK3B31 group, and Veillonella (p < 0.05). Alistipes, Monoglobus , and Veillonella were more abundant in the BMA group, whereas the Prevotellaceae NK3B31 group showed higher abundance in the control group, consistent with the results of the LEfSe analysis. No serious adverse events were observed in either group during the study period. BMA demonstrated clinically meaningful efficacy and good tolerability in patients with mild-to-moderate atopic dermatitis. These findings suggest that BMA may be a safe and effective complementary therapeutic option for AD management. Additionally, changes in the gut microbiome were observed, which may offer insights into the potential mechanisms underlying its therapeutic effects.