Gastrointestinal (GI) illnesses are associated with various environmental factors, such as water quality, stormwater runoff, agricultural runoff, sewer overflows, and wastewater treatment plant effluents. However, rather than assessing an individual factor alone, two indices incorporating a combination of ecological and environmental stressors were created to represent (1) overall watershed integrity, Index of Watershed Integrity (IWI) and (2) catchment integrity, Index of Catchment Integrity (ICI). These indices could provide a more comprehensive understanding of how watershed/catchment integrity potentially impact the rates of GI illness, compared to assessing an individual stressor alone. We utilized the IWI and ICI, as well as agricultural and urban land uses, to assess associations at the county level with the rates of GI illness in a population of adults over 65 years of age. Our findings demonstrated that both watershed and catchment integrity are associated with reduced hospitalizations for any GI outcomes, though association varied by urbanicity. We believe that improved versions of the IWI and ICI may potentially be useful indicators for public health analyses in other circumstances, particularly when considering rural areas or to capture the complex stressors impacting the ecological health of a watershed.