Background: HIV/AIDS prevention has been widely adopted worldwide, but little is known about HIV/AIDS knowledge and attitudes in the Arabian Peninsula. Aim: To summarize the level of knowledge and attitude about HIV/AIDS in seven Arabian Peninsula countries (Saudi Arabia, Oman, Kuwait, Qatar, Bahrain, Yemen, and the United Arab Emirates (UAE)). Methods: A systematic literature search was performed using combined keywords in four scientific databases of peer-reviewed publications from January 2010 to June 2019. Twenty-five articles were included in the systematic review, and twenty studies in the meta-analysis. The data was analyzed using a random-effect model due to the heterogeneity between the studies. Results: Seventeen studies reported on the level of knowledge and overall knowledge about HIV/AIDS in this region: 74.4% (95% confidence interval (CI): 66.8%–82.0%, p 0.001) and the attitude was 52.8% (95% CI: 36.9%–68.6%, p 0.001). A study from Oman reported higher knowledge levels (95.5%, 95% CI: 94.2%–96.8%) while less than a quarter of the Bahrain population had positive attitudes 22.5% (95% CI: 20.5%–24.5%). Medical doctors showed higher knowledge (94.1%, 95% CI: 92.9%–95.3%), but a positive attitude was only observed in 32.5% (95% CI: 28.8%–36.2%) of the dentists toward HIV/AIDS. Conclusion: The overall knowledge about HIV/AIDS was found to be satisfactory (74.4%), but about half (52.8%) of those displayed negative attitudes toward HIV/AIDS. Regular training courses as well as reviewing and reinforcing HIV/AIDS prevention guidelines can be useful to update knowledge and improve attitudes in this region.