Chlorine spraying was widely used during filovirus outbreaks, but concerns about occupational health risks led to a shift toward wiping. This systematic review aimed to evaluate the health risks associated with exposure to disinfectants among healthcare workers (HCWs), with a specific focus on chlorine-based products and spraying compared to alternative disinfectants and general disinfection tasks (GDTs). PubMed, Embase, and Scopus were searched from inception to March 2025. Eligible studies included observational or experimental research on HCWs exposed to chemical disinfectants. Two reviewers independently screened studies, assessed the risk of bias using a validated occupational health tool, and evaluated evidence certainty with the GRADE approach. Meta-analyses used fixed- and random-effects models; heterogeneity was assessed with I² statistics. Out of 7154 records, 29 studies were included. Most studies were cross-sectional with a high bias risk. Odds ratios (ORs) were calculated using non-exposed groups as reference. Significant associations with respiratory conditions were found for chlorine-based products (OR 1.71), glutaraldehyde (OR 1.44), spraying (OR 2.25), and GDTs (OR 2.20). Exposure to chlorine-based products, glutaraldehyde, spraying, and GDTs likely increases respiratory risk in HCWs, as supported by moderate-certainty evidence. These findings support prioritizing safer disinfectants and strengthening protective measures over banning specific application methods.