Purpose Worldwide, in the last decade, the numbers of new HIV infections and AIDS-related deaths have drastically decreased. Despite that, around 18 million infected individuals receive antiretroviral therapy and thus tend to live longer. This cross-sectional study was conducted to assess the level of HIV-related knowledge among undergraduate dental students at Ain Shams University (ASU) in Cairo, Egypt and to determine their attitudes toward treating HIV-positive patients. Methods The study sample included 247 undergraduate dental students of third, fourth, and fifth academic years at the Faculty of Dentistry, ASU who were randomly selected to participate in this survey. Data were collected using a self-administrated anonymous questionnaire. Chi square and ANOVA tests were used to measure differences in the level of knowledge and attitudes among students of the 3 years. Multiple linear regression analysis was performed with 95% confidence interval. Results Within the students’ population, around 94% incorrectly considered dentists to be at high risk of acquiring HIV infection and 47% believed that saliva is a vehicle for its transmission. Moreover, the majority of students were unaware of the association between HIV and common oral manifestations such as oral candida, Kaposi sarcoma, and leukoplakia. Although 69% of the students were willing to deliver oral care to people living with HIV (PLHIV), only 33% perceived themselves knowledgeable enough to do so. Conclusion Dental students were not adequately prepared to recognize and manage HIV-positive individuals. Thus, better education and training are required to raise their levels of HIV-related knowledge and enhance their capabilities to treat PLHIV.