We need a range of bioindicators in environmental risk assessment from contaminants in the ecosystem. Molluscs being the second-largest animal phylum, and with great ecological and economic value makes them an ideal bioindicator. This study aimed to evaluate if laboratory-bred Potamopyrgus antipodarum has the potential to show the impact of contaminants from different land-use activities and/or degree of pollution on a freshwater ecosystem. This work assessed the impact of contaminants arising from runoff and or direct discharges in Merri Creek by measuring both organism-level responses (survival, growth, and reproduction), and sub-organism level responses (glutathione S-transferase (GST) activity, lipid peroxidation (LPO) activity, and catalase (CAT) activity) in snails after 28-d of deployment. The snails were deployed at nine sites in Merri Creek and one site in Cardinia Creek. The top two sites in Merri Creek with low impacts from human activities were reference sites, while seven sites were impacted by various anthropogenic land uses. Cardinia Creek (additional reference site) had lower human activity. High concentrations of heavy metals, nutrients, and/or synthetic pyrethroids (bifenthrin) dominated these sites, which are likely to have contributed to the negative responses observed in the snails. There was little influence from environmental conditions and site location on the endpoints because similarity in response was observed at an additional reference site in comparison to the reference sites in Merri Creek. At the organism level, reproduction increased and/or reduced, while CAT was affected at the sub-organism level. Thus, P antipodarum has the potential to be a sensitive bioindicator for Australian conditions because a number of responses were observed in the snails to varying concentrations of contaminants across different land-use activities and showed similar sensitivity to population found in other regions of the globe and other bioindicators.