Background Digital health interventions (DHIs) are effective in improving poor nutrition, physical inactivity, overweight and obesity. There is evidence suggesting that the impact of DHIs may be enhanced by improving user engagement. However, little is known about the overall effectiveness of strategies on engagement with DHIs. Objective This study aims to assess the overall effectiveness of strategies to improve engagement with DHIs targeting nutrition, physical activity, and overweight or obesity and explore associations between strategies and engagement outcomes. The secondary aim was to explore the impact of these strategies on health risk outcomes. Methods The MEDLINE, Embase, PsycINFO, CINAHL, CENTRAL, Scopus, and Academic Source Complete databases were searched up to July 24, 2023. Eligible studies were randomized controlled trials that evaluated strategies to improve engagement with DHIs and reported on outcomes related to DHI engagement (use or user experience). Strategies were classified according to behavior change techniques (BCTs) and design features (eg, supplementary emails). Multiple-variable meta-analyses of the primary outcomes (usage and user experience) were undertaken to assess the overall effectiveness of strategies. Meta-regressions were conducted to assess associations between strategies and use and user experience outcomes. Synthesis of secondary outcomes followed the “Synthesis Without Meta-Analysis” guidelines. The methodological quality and evidence was assessed using the Cochrane risk-of-bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation tool respectively. Results Overall, 54 studies (across 62 publications) were included. Pooled analysis found very low-certainty evidence of a small-to-moderate positive effect of the use of strategies to improve DHI use (standardized mean difference=0.33, 95% CI 0.20-0.46; P<.001) and very low-certainty evidence of a small-to-moderate positive effect on user experience (standardized mean difference=0.29, 95% CI 0.07-0.52; P=.01). A significant positive association was found between the BCTs social support (effect size [ES]=0.40, 95% CI 0.14-0.66; P<.001) and shaping knowledge (ES=0.39, 95% CI 0.03-0.74; P=.03) and DHI use. A significant positive association was found among the BCTs social support (ES=0.70, 95% CI 0.18-1.22; P=.01), repetition and substitution (ES=0.29, 95% CI 0.05-0.53; P=.03), and natural consequences (ES=0.29, 95% CI 0.05-0.53; P=.02); the design features email (ES=0.29, 95% CI 0.05-0.53; P=.02) and SMS text messages (ES=0.34, 95% CI 0.11-0.57; P=.01); and DHI user experience. For secondary outcomes, 47% (7/15) of nutrition-related, 73% (24/33) of physical activity–related, and 41% (14/34) of overweight- and obesity-related outcomes reported an improvement in health outcomes. Conclusions Although findings suggest that the use of strategies may improve engagement with DHIs targeting such health outcomes, the true effect is unknown because of the low quality of evidence. Future research exploring whether specific forms of social support, repetition and substitution, natural consequences, emails, and SMS text messages have a greater impact on DHI engagement is warranted. Trial Registration PROSPERO CRD42018077333; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=77333