Nanoplastics (NPs) pollution is a global issue posing potential threats to human health, particularly the digestive system. NPs may exacerbate intestinal inflammation, increasing the risk of inflammatory bowel disease. However, the impact of intestinal peristalsis on NP‐induced inflammation remains unknown. Here, a biomimetic gut‐on‐a‐chip (GOC) with integrated online sensing is presented to investigate NPs' impact on intestinal inflammation and propose enhanced peristalsis as a potential intervention. The GOC simulates intestinal peristalsis through periodic stretching and the optimized sensors dynamically detect inflammatory cytokines interleukin‐6 (IL‐6) and tumor necrosis factor alpha (TNF‐α) over 12 d with low detection limits (0.0095 and 0.0020 pg mL−1). Exposure to NPs led to vacuolization, apoptosis, and loss of tight junction proteins in intestinal cells, with IL‐6 and TNF‐α secretion peaking at 24 h (1341.55 ± 64.91 and 862.03 ± 66.45 pg mL−1). Notably, increasing periodic strain alleviates inflammatory cytokines secretion induced by NPs. With strain increased from 5% to 6.5%, IL‐6 and TNF‐α secretion decrease by 2.73‐fold and 3.34‐fold, respectively. This highlights the protective role of intestinal peristalsis in reducing NP‐induced inflammation.