Gastrointestinal (GI) neuromuscular diseases can be challenging to diagnose due to inadequate profiling technologies that are unable to pinpoint underlying pathology. We introduce a luminal electrophysiological neuroprofiling system (LENS). This tool uses high-resolution electromyographic data to capture motility of the GI tract, grade neurogenic deficiencies over time, and elucidate motility patterns. Through the development of analytical metrics, we determine “neuroprofiles” for various enteric neuropathies in models of dysmotility, sphincter dysfunction, and aganglionosis. The LENS differentiates between aganglionic and ganglionic regions based on the contractile rate (p < 0.0001) and root-mean-square amplitude (p < 0.0001). In mice with hypomotility, metrics like area under the curve and peak height of the Fourier transformation of the electrophysiological signal in the frequency ranges of 0–20 and 115–135 Hz were significant differentiators, with up to 89% accuracy of classification between pathologic and normal motility. Such a platform can enable realization of specific diagnoses and quantify their severity.