Transfusions and blood donations are relatively risk-free medical procedures. However, attitudes, beliefs, and knowledge levels about blood donation and transfusion may influence such operations. This systematic review aims to comprehensively investigate the level of knowledge and attitudes towards blood donation in Saudi Arabia. PubMed, Scopus, Web of Science, and ScienceDirect were systematically searched for relevant literature. Rayyan (Qatar Computing Research Institute, Ar-Rayyan, Qatar) was employed throughout this comprehensive process. This review included 17 studies with a total of 9,212 patients, and 4,806 (52.2%) were males.The majority of Saudis lacked awareness about blood donation and had unfavorable opinions towards it. In addition to various fears, mistrust, a lack of information, and not being approached by anyone to donate blood, participants reported that the distance to the donation site, the difficulty with transportation, the time commitment, getting a quick break from work or the office, or taking time off from home were also contributing to the negative attitudes towards blood donation. While youthful participants were more likely to contribute, Saudi university students in this study had inadequate information but positive attitudes about blood donation. Ineligibility, fear of giving blood, and inaccurate information regarding blood donation are the main deterrents to blood donation.