The COVID-19 pandemic has renewed interest in propolis products worldwide. Propolis components have inhibitory effects on the ACE2, TMPRSS2 and PAK1 signaling pathways; in addition, antiviral activity has been proven in vitro and in vivo. In pre-clinical studies, propolis promoted immunoregulation of pro-inflammatory cytokines, including reduction in IL-6, IL-1 beta and TNF-α. Standardized propolis products with consistent bioactive properties are now available, a standardized green propolis extract (EPP-AF®). In a randomized, controlled, open-label, single-center trial, hospitalized adult COVID-19 patients were treated with EPP-AF® as an adjunct therapy. Patients were allocated to receive standard care plus an oral dose of 400 mg or 800 mg/day of green propolis EPP-AF® for seven days, or standard care alone. Standard care included all necessary interventions, as determined by the attending physician. We enrolled 124 patients in total. The length of hospital stay post-intervention was shorter in both propolis groups than in the control group; lower dose, median 7 days versus 12 days (95% confidence interval [CI] −6.23 to −0.07; p = 0.049) and higher dose, median 6 days versus 12 days (95% CI −7.00 to −1.09; p = 0.009). In the high dose propolis group, there was a lower rate of acute kidney injury than in the controls (4.8 vs 23.8%), (odds ratio [OR] 0.18; 95% CI 0.03–0.84; p = 0.048). Consequently, we conclude that propolis can reduce the impact of COVID-19.