Background Excessive plantar pressure leads to increased risk of diabetic foot ulcers. Diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) have been considered to be associated with alterations in gait and plantar pressure in diabetic patients. However, few studies have differentiated the effects with each of them. Objective To investigate the plantar pressure distribution in diabetic patients, with DPN and PAD as independent or combined factors. Methods 112 subjects were recruited: 24 diabetic patients with both DPN and PAD (DPN-PAD group), 12 diabetic patients with DPN without PAD (DPN group), 10 diabetic patients with PAD without DPN (PAD group), 23 diabetic patients without DPN or PAD, and 43 nondiabetic healthy controls (HC group). The in-shoe plantar pressure during natural walking was measured. Differences in peak pressure, contact area, proportion of high pressure area (%HP), and anterior/posterior position of centre of pressure (COP) were analysed. Results Compared with HC group, in DPN-PAD group and DPN group, the peak pressures in all three forefoot regions increased significantly; in PAD group, the peak pressure in lateral forefoot increased significantly. The contact area of midfoot in the DPN-PAD group decreased significantly. PAD group had larger HP% of lateral forefoot, DPN group had larger HP% of inner forefoot, and DPN-PAD group had larger HP% of total plantar area. There was a significant tendency of the anterior displacement of COP in the DPN-PAD group and DPN group. No significant differences were observed between the D group and HC group. Conclusion DPN or PAD could affect the plantar pressure distribution in diabetic patients independently or synergistically, resulting in increased forefoot pressure and the area at risk of ulcers. DPN has a more pronounced effect on peak pressure than PAD. The synergistic effect of them could significantly reduce the plantar contact area of midfoot.