<p>Agrochemicals such as fertilizers and pesticides are vital for boosting crop yields and managing pests, yet their misuse threatens human health, soil ecosystems, and biodiversity, particularly in sensitive wetlands. This study assessed smallholder farmers’ knowledge, perceptions, and practices regarding the use of agrochemicals in Kampala’s peri-urban wetlands. It examined the effects of two commonly used pesticides, Rocket (profenofos + cypermethrin) and Dudu Acelamectin (abamectin + acetamiprid), on soil microbial diversity and activity. Using a mixed-methods design, data were collected from 100 farmers across Bugolobi, Kasokoso, and Kinawataka wetlands, with laboratory analyses conducted on soil samples from the Lubiji–Nsooba wetland. Fewer than half of the farmers used agrochemicals, often relying on personal experience rather than professional guidance. Poor label literacy, limited use of protective gear, and unsafe storage or disposal practices were widespread. Agrochemical use was significantly associated with income, training, and crop type. Laboratory results showed that Rocket increased fungal populations, while Dudu Acelamectin enhanced bacterial, fungal, and actinomycete growth, particularly at higher concentrations. Microbial phosphorus and nitrogen peaked at moderate doses, whereas carbon declined with Rocket. These findings highlight the need for improved farmer education, safer pesticide handling, and wetland-specific pesticide regulations to safeguard soil microbial health and ecosystem sustainability.</p>