Abstract Objective We examine the preliminary impact of group-cognitive behavioral therapy (G-CBT) versus a family-strengthening intervention delivered via multiple family group (MFG) in improving ART adherence among adolescents living with HIV (ALHIV) in Uganda. Methods We analyzed data from a pilot cluster-randomized trial (2020–2022) conducted in 9 clinics in Uganda among 89 participants, who were eligible out of the 147 ALHIV screened. Participants were eligible if they were aged 10–14 years, HIV positive, taking ART, and living with a family. Adolescents were randomized, at the clinic level, to receive the usual care (n = 29), MFG (n = 34), or G-CBT (n = 26). The interventions were delivered over 3 months. Overall, the mean percentage attendance for the 10 G-CBT and MFG sessions was 87.7% and 90.2%, respectively. Three ALHIV were lost to follow-up, while 1 child died. Adherence was assessed using pharmacy records collected at baseline and 4 additional pharmacy visits. We used mixed-effects logistic regression analysis to examine the effect of the interventions on ART adherence. Results We found statistically significant main effects for the intervention, χ2(2) = 7.76, p = .021, time, χ2(2) = 39.67, p < .001, and intervention–time interaction effect χ2(6)= 27.65, p < .001. Pairwise comparisons showed increasing adherence in the MFG group compared to usual care at visit 3 (odds ratio [OR] = 4.52 [1.01–20.11], p = .047) and visit 5 (OR = 3.56 [1.42–8.91], p = .007). Also, compared to usual care, participants who received G-CBT showed higher adherence at visit 4 (OR = 2.69 [1.32–5.50], p = .007). Conclusions Our study showed preliminary evidence that G-CBT and MFG might have contributed to improved ART adherence among ALHIV. Moreover, G-CBT is a low-cost alternative to expensive individual therapy, especially in low-resource settings. The results warrant the need for more extensive studies to better understand the role of these interventions in the routine care of ALHIV. The trial is registered at ClinicalTrials.Gov (#NCT04528732).