A recent study amongst South African dental students found that a number of them had perceived moderate to severe stress and as a result, some have resorted to stimulant drugs. The aim of the study was to assess substance use by dental and oral hygiene students at a university in South Africa. A cross-sectional design was used and all dental and oral hygiene students registered in 2019 at a university in South Africa were asked to participate. Materials and Methods A pretested, validated self-administered questionnaire was used to achieve the aim. The objectives were to identify which substances were used, where they were obtained, frequency and reasons for use, as well as the self-perceived benefits and side effects experienced. Data was analysed using SPSS version 27. The data was confidential and anonymity was ensured. A total of 303 (88%) agreed to participate with ages from 17 to 36 years and a mean of 22.3 years. Over two thirds 206 (67.9%) used substances. Almost half of the group (44.6%) took one product, 16.5% took two, and 7% consumed between 3 and 5. The sources of substances ranged from peers, friends, acquaintances and pharmacies. Nearly twenty percent of the students used caffeine products, energy drinks, and methylphenidate. Almost 10% used anti-anxiety pills and anti-depressants whilst just above 11% used natural boosters and multivitamins. More than half of the students used the substances to stay awake and improve marks and 45(22%) of the users struggled to stop. Conclusions Over two thirds of students used substances, with almost half using one substance. There were multiple sources of substances. More than half of the students used them to stay awake and improve marks.