Despite the frequent use of prophylactic antibiotics in hospitals for extracorporeal membrane oxygenation (ECMO) patients, the Extracorporeal Life Support Organization (ELSO) Infectious Disease Task Force does not recommend routine antibiotic prophylaxis due to a lack of compelling evidence. We assessed the effectiveness of prophylactic antibiotics in ECMO patients. We conducted a comprehensive search of multiple databases from their inception up to September 6, 2023, on various databases using keywords like “antibiotics,” “prophylaxis,” “extracorporeal membrane oxygenation,” and “ECMO.” Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included research. We collected data using Microsoft Excel version 2016, mean and standard deviations were calculated for continuous data, while frequencies and percentages were calculated for binomial data. A total of three studies was included in the review with a total of 8,954 participants, of which 4,483 (50.06%) received antibiotic prophylaxis, and 1,131 (25.22%) were female. The administration of antibiotics prophylactically was associated with reduction in rate of mortality, the risk of infections, and complications like acute kidney injury and diarrhea. Although there have been some benefits on antibiotic prophylaxis, prospective research, and possibly the creation of tailored, ECMO-specific bundles will be needed to identify efficient ways to prevent ECMO infection.