Consumers nowadays are becoming more aware of the importance of using only meat products containing safe and natural additives. Hence, using natural food additives for extending the shelf life of meat along with delaying microbial growth has become an urgent issue. Given the increasingly popular view of Moringa oleifera leaves as a traditional remedy and also the scarcity of published data concerning its antimicrobial effect against foodborne pathogens in meat and meat products, we designed the present study to investigate the antimicrobial effect of Moringa oleifera leaves aqueous extract (0.5%, 1%, and 2%) on ground beef during refrigerated storage at 4 °C for 18 days. MLE revealed potent antimicrobial properties against spoilage bacteria, such as aerobic plate count and Enterobacteriaceae count. MLE 2% showed a significant (p < 0.01) reduction in the counts of E. coli O157:H7, Salmonella enterica serovar Typhimurium, and Staphylococcus aureus artificially inoculated to ground beef by 6.54, 5.35, and 5.40 log10 CFU/g, respectively, compared to control, by the 18th day of storage. Moringa leaves extract (MLE) had no adverse effect on the overall acceptability and other sensory attributes; moreover, it induced a slight improvement in the tenderness and juiciness of treated ground beef, compared to the control. Therefore, MLE can be used as a healthy, natural, and safe preservative to increase meat products’ safety, quality, and shelf stability during cold storage. A promising approach for using natural food additives rather than chemical preservatives could begin new frontiers in the food industry, as they are more safe and do not constitute health risks to consumers.