Integrating digital interventions in healthcare has gained increasing popularity among clinical pharmacists (CPs) due to advances in technology. The purpose of this study was to systematically review CP-led digital interventions to improve patients' health-related clinical outcomes. PubMed and the Cochrane Database were searched to select studies that had conducted a randomized controlled trial to evaluate clinical outcomes in adults following a CP-led digital intervention for the period from January 2005 to August 2021. A total of 19 studies were included in our analysis. In these 19 studies, the most commonly used digital intervention by CPs was telephone use (n = 15), followed by a web-based tool (n = 2) and a mobile app (n = 2). These interventions were provided to serve a wide range of purposes in patients' outcomes: change in lab values (e.g., blood pressure, HbA1c) (n = 23), reduction in health service use (n = 8), enhancing adherence (n = 6), improvement in drug-related outcomes (n = 6), increase in survival (n = 3), and reduction in health-related risk (e.g., CVD risk) (n = 2). Although the impacts of telephone-based interventions on patients' outcomes were decidedly mixed, web-based interventions and mobile apps exerted generally positive influences. To date, little research has investigated the cost-effectiveness of digital interventions. Future studies are warranted.