Globally, nail salons represent a fast expanding industry and often with low-income cosmeticians. In general, cosmeticians have limited access to safety information about the hazardous materials they handle, which would potentially enable them to minimize workplace exposures. The problem is much pronounced in low- and middle-income countries due to weaknesses in regulation of the industry. We investigated determinants of exposures to hazardous materials among nail cosmeticians in Kampala District, Uganda. We employed a cross-sectional study design among a random sample of 243 participants. The sociodemographic characteristics, education and training status, knowledge about routes of exposure to hazardous chemicals, and personal protective material use of cosmeticians were assessed through face-to-face interviews. Most cosmeticians were aged 18–34 years, and more males were engaged in this work than females. Also, 82.7% believed inhalation was the major exposure route for the chemicals they handled. Participants who had attained secondary-level education and above were over three times more likely to wear masks (AOR = 3.19, 95% CI 1.58–6.41) and gloves (AOR = 3.48, 95% CI 1.55–7.81) and over two times more likely to use aprons (AOR = 2.50, 95% CI 1.18–5.32). Participants who had ever received safety training on hazardous chemicals were more likely to wear all four personal protective equipment: masks (AOR = 3.21, 95% CI 1.61–6.42), gloves (AOR = 4.23, 95% CI 2.05–8.75), goggles (AOR = 4.14, 95% CI 1.25–13.65), and aprons (AOR = 2.73, 95% CI 1.25–5.96). Participants who had spent more than two years in the nail cosmetics business were more likely to wear masks (AOR = 3.37, 95% CI 1.64–6.95). With the increasing demand for nail cosmetics, and many people in urban areas of low-income countries engaging in this industry, there is need for training and better workplace policies to promote a healthier urban workforce dealing in cosmetics.