Global Human papillomavirus (HPV) vaccination rates remain low despite available WHO-approved vaccines. Digital interventions for promoting vaccination uptake offer a scalable and accessible solution to this issue. Here we report a systematic review and meta-analysis examining the efficacy of digital interventions, comparing educational and reminder approaches, for promoting HPV vaccination uptake (HVU). This study also identifies factors influencing the effectiveness of these interventions. We searched PubMed, PsycInfo, Web of Science, and the Cochrane Library from each database’s inception to January 2023. Three raters independently evaluate the studies using a systematic and blinded method for resolving disagreements. From 1929 references, 34 unique studies (281,280 unique participants) have sufficient data. Client reminder (OR, 1.41; 95% CI, 1.23–1.63; P < 0.001), provider reminder (OR, 1.39; 95% CI, 1.11–1.75; P = 0.005), provider education (OR, 1.18; 95% CI, 1.05–1.34; P = 0.007), and client education plus reminder interventions (OR, 1.29; 95% CI, 1.04–1.59; P = 0.007) increase HVU, whereas client education interventions do not (OR, 1.08; 95% CI, 0.92–1.28; P = 0.35). Digital intervention effectiveness varies based on participants’ gender and the digital platform used. Interventions targeting male or mixed-gender participants demonstrate greater benefit, and reminder platforms (SMS, preference reminders, or electronic health record alerts) are more effective in increasing HVU. Digital interventions, particularly client and provider reminders, along with provider education, prove significantly more effective than client education alone. Incorporating digital interventions into healthcare systems can effectively promote HPV vaccination uptake. Reminder interventions should be prioritized for promoting HVU.