Multivariate polynomial regression (MPR) models were developed for five macrophyte indices. MPR models are able to capture complex interactions in the data while being tractable and transparent for further analysis. The performance of the MPR modeling approach was compared to previous work using artificial neural networks. The data were obtained from hydromorphologically modified Polish rivers with a widely varying water quality. The modeled indices were the Macrophyte Index for Rivers (MIR), the Macrophyte Biological Index for Rivers (IBMR), and the River Macrophyte Nutrient Index (RMNI). These indices measure the trophic and ecological status of the rivers. Additionally, two biological diversity indices, species richness (N) and the Simpson index (D), were modeled. The explanatory variables were physico-chemical properties depicting water quality and river hydromorphological status indices. In comparison to artificial neural networks, the MPR models performed similarly in terms of goodness of fit. However, the MPR models had advantages such as model simplicity and ability to be subject to effective visualization of complex nonlinear input–output relationships, as well as facilitating sensitivity analysis using importance ratios to identify effects of individual input variables.