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Antibiotic resistance has become an increasingly common problem in treating infectious diseases caused by pathogenic micro-organisms, and this threat is heightened due to the lack of new antibiotic discoveries since the 1980s. This paper aims to summarise the currently available knowledge on the antimicrobial properties of cholesterol esters and to evaluate the use of cholesterol esters as an alternative to antibiotics. A systematic literature search was conducted in three databases namely Pubmed, Embase, and Web of Science to retrieve articles published between 2000 and 2020 where cholesterol esters were the primary or one of the primary examined molecules as part of research targeting immunity and antimicrobial operations. The findings showed antibacterial properties of cholesterol esters, their synergistic activity with antibiotics, antimicrobial role of cholesterol esters in upper respiratory tract and its diseases in humans, and correlation of cholesterol esters with infection protection in physically active individuals. Overall, there is strong evidence that cholesterol esters have antimicrobial properties. However, the currently pooled information available for cholesterol esters’ antimicrobial properties is not expansive enough to draw a conclusion on its ability to replace existing antibiotics as a treatment for infections and this warrants future investigation.