Brain functional alterations in type 2 diabetes with diabetic peripheral neuropathy (DPN) related to motor dysfunction remain largely unknown. We aimed to explore intrinsic resting brain activity in DPN. A total of 28 patients with DPN, 43 patients with diabetes and without DPN (NDPN), and 32 healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging. We calculated the amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo). One-way analysis of covariance was applied to evaluate the above indicators among the 3 groups, and the mean ALFF/fALFF/ReHo values of altered brain regions were then correlated with clinical features of patients. Compared with the NDPN group, the DPN group showed significantly decreased ALFF values in the right orbital superior frontal gyrus (ORBsup) and medial superior frontal gyrus (SFGmed), and increased ALFF values in the left inferior temporal gyrus (ITG) and decreased fALFF values in the right SFGmed. Compared with HCs, the NDPN group showed increased ALFF values in the right ORBsup, middle frontal gyrus, and left orbital middle frontal gyrus, and decreased fALFF values in the right middle temporal gyrus. Notably, the mean ALFF values of the right ORBsup were significantly negatively correlated with Toronto Clinical Scoring System scores and gait speed in diabetics. The mean ALFF/fALFF values of right SFGmed and the mean ALFF values of left ITG and right ORBsup were significantly differentiated between DPN and patients witht NDPN in receiver operating characteristic curve analysis. Patients with DPN have abnormal brain activity in sensorimotor and cognitive brain areas, which may implicate the underlying neurophysiological mechanisms in intrinsic brain activity.