Sepsis presents a significant medical challenge due to its intense inflammatory response to infection, often resulting in high mortality rates. A promising therapeutic strategy targets the cholinergic anti-inflammatory pathway (CAIP), which regulates immune responses. This study investigates the ingestion of piezoelectric particles that adhere to the stomach lining, specifically targeting TRPV1 receptors. In a mouse model of sepsis, these particles, when activated by low-intensity pulsed ultrasound, generate mild electrical pulses. These pulses stimulate vagal afferent fibers, transmitting signals to the brain and modulating the neural-immune network via the CAIP. Consequently, this leads to a reduction in systemic inflammation, mitigating weight loss, alleviating multiple tissue injuries, and preventing death by modulating immune cells in the spleen. This approach addresses the critical need for noninvasive sepsis therapies, potentially improving patient outcomes. Utilizing portable ultrasound equipment with minimal thermal effects, this technique offers a safe and convenient treatment option, even for home use.