The involvement of the Enteric Nervous System (ENS) in digestive and neurological disorders is widely recognized and constitutes a novel target for diagnostic biomarkers and therapies. For example, Parkinson’s disease patients are now stratified according to gut-first or brain-first patterns that diverge in symptom progression. However, large-scale characterization of this neuronal network is often limited to local sampling that cannot reflect network dynamics. We present a new method for minimally invasive in-vivo intraluminal investigation of electrophysiological activity from the entire distal mouse colon. Our device is a miniature endoscope patterned with recording sites spaced to optimally address the distribution of enteric ganglia. It can deliver other endoscopic accessories as may be required, for example for drug infusions or fiber optic delivery for optogenetic stimulation. During recording sessions lasting up to one hour we were able to reliably register and characterize colonic electrophysiological patterns in anesthetized mice. We observed a typical default activity consisting of ~20 s trains of neurogenic spike bursts every ~1 s, the trains themselves interspersed by ~30 s periods of silence, with such activity patterns being highly orchestrated across long sections of the colon. The default activity patterns were readily and rapidly manipulated by compounds modulating specific neurotransmitter effects, such as donepezil or atropine with respect to acetylcholine. In the future, the developed methodology will be applied in both healthy animals and animals with morphological and functional impairment of ENS with the aim to compare colonic enteric network activity.