Plastic waste is a pernicious environmental pollutant that threatens ecosystems and human health by releasing contaminants including di(2-ethylhexyl) phthalate (DEHP) and bisphenol A (BPA). Therefore, a machine-learning (ML)-powered electrochemical aptasensor was developed in this study for simultaneously detecting DEHP and BPA in river waters, particularly to minimize the electrochemical signal errors caused by varying pH levels. The aptasensor leverages a straightforward and effective surface modification strategy featuring gold nanoflowers to achieve low detection limits for DEHP and BPA (0.58 and 0.59 pg/mL, respectively), excellent specificity, and stability. The least-squares boosting (LSBoost) algorithm was introduced to reliably monitor the targets regardless of pH; it employs a layer that adjusts the number of multi-indexes and the parallel learning structure of an ensemble model to accurately predict concentrations by preventing overfitting and enhancing the learning effect. The ML-powered aptasensor successfully detected targets in 12 river sites with diverse pH values, exhibiting higher accuracy and reliability. To our knowledge, the platform proposed in this study is the first attempt to utilize ML for the simultaneous assessment of DEHP and BPA. This breakthrough allows for comprehensive investigations into the effects of contamination originating from diverse plastics by eliminating external interferent-caused influences.