Appendicitis is one of the most common gastrointestinal conditions a person can develop. Throughout the years of assessing the different focuses of appendicitis, such as origin, symptoms, labs, diagnosis, treatment, and complications, there have been mere mentions of sex differences. One of the most known sex differences in appendicitis is the fact that males are significantly more likely to develop appendicitis compared to females. Another postulated difference is that males may be more likely to develop a perforated appendix. These differences significantly affect the various aspects of diagnosing and treating appendicitis and may even influence the outcome of appendicitis. Sex difference analysis of conditions has been widely researched over the last two decades, and sex can influence and impact conditions from initial presentation to the outcome of treatment. This paper evaluates the sex differences in appendicitis concerning incidence, risk factors, symptoms, diagnosis technique, treatment, and outcomes across ages. Following PRISMA guidelines, this systematic review reviewed PubMed, ScienceDirect, and ProQuest databases for articles pertaining to sex differences in appendicitis. The original article count was 21,121, which was narrowed down to 28 publications. It was found that, as previously described, males had a significantly higher rate of appendicitis, as well as were at significant risk of perforated appendicitis. No official risk factors were found to differ between the sexes, but males were more likely to complain of symptoms like right lower quadrant cramps/tenderness/pain and loss of appetite. Scores such as the pediatric appendicitis score (PAS) and Ohmann have been used to diagnose appendicitis, but the PAS was significantly more accurate for females, and the Ohmann resulted in significantly fewer negative appendectomies in females as well. Ultrasound and computed tomography (CT) are still the gold standards for diagnosis; however, while time to CT was significantly delayed in females, they were more likely to undergo extensive imaging, possibly to rule out other conditions. Males were more likely to undergo open appendectomies compared to females, who more frequently underwent laparoscopic appendectomy, yet females were more likely to experience complications. Further research should evaluate the influences that can predict postoperative outcomes following appendectomies between sexes and how to prevent/reduce their occurrence.