Pharmaceutical effluents (PE) are liquid wastes produced during pharmaceutical manufacturing. These effluents can alter the physico-chemical characteristics (PSC) of water and can affect the plankton communities inhabiting such aquatic environments. The Okun Stream in Ilorin, Kwara State, Nigeria, receives PE from a pharmaceutical company. Three sampling locations—upstream, point of effluent discharge (POD), and downstream—spaced 500 meters apart, were sampled biweekly from January to June. Temperature, pH, and dissolved oxygen (DO) were measured in situ. Heavy metals (HM) were analyzed using standard digestion and laboratory methods. Plankton were collected using a plankton net and identified using standard taxonomic guidelines. PSC and HM data were analyzed using ANOVA. Principal component analysis (PCA) was used to examine correlations between PSC and HM across sampling locations. Canonical correlation analysis (CCA) was employed to explore the relationships between PSC, HM, and plankton communities. Plankton diversity indices were calculated, and Pearson's correlation coefficients were used to assess the relationships between PSC, HM, and plankton abundance. At the POD, DO levels were low (2.24 ± 0.87mg/ L). Across all sampling sites, iron (Fe) was the most abundant heavy metal, while lead (Pb) was the least. Among phytoplankton, Cyanophyceae were the most dominant, with relative abundances of 38.74, 38.4, and 43.68% at the upstream, POD, and downstream stations, respectively. Among zooplankton, Protozoans were most abundant, with values of 60.98, 61.65, and 63.12% at the respective stations. Zooplankton Shannon diversity indices of 0.6689 (upstream), 0.6657 (POD), and 0.7184 (downstream) indicate that the Okun Stream is heavily polluted. To mitigate pollution and protect aquatic life, the pharmaceutical company should implement proper effluent treatment before discharge. Additionally, local residents should reduce anthropogenic activities that contribute to waste inflow into the stream.