The COVID-19 pandemic and other infectious diseases continue to threaten public health, particularly in densely populated informal settlements. Effective hand hygiene, supported by alcohol-based hand sanitizers (ABHS), plays a critical role in preventing disease transmission. This study assessed the quality, safety, and compliance of ABHS used in informal settlements around Cape Town. A total of 78 samples were collected from spaza shops, with 72 analyzed using gas chromatography with flame ionization detection. The results showed that 76% of ethanol-based sanitizers met compliance standards, while 24% did not. Isopropanol compliance (≥70%) was only observed in 36% of samples, with 64% failing to meet Centers for Disease Control and Prevention (CDC) guidelines. Overall, 74% of hand sanitizers complied with recommended alcohol concentrations by the U.S. Food and Drug Administration (FDA) and CDC, while 26% posed a health risk due to non-compliance. These findings emphasize the urgent need for stricter regulation and public education to ensure effective hand sanitizers are used, thereby reducing infection risks in vulnerable populations. The study aims to inform public health policies and improve regulatory standards.