Premature infants often cannot successfully and coordinately complete their oral feeding. Mature sucking, swallowing, and respiration activities are crucial indicators for the survival of newborn infants. Due to the vulnerability and unobvious muscle activities of premature infants, current clinical care givers mainly depend on the subjective behavioral observation of infants during oral feeding. There is still lack of an integrated oral feeding monitoring system to objectively and quantifiably monitor the related physiological parameters of premature infants. In this study, a wireless multi-parameter monitoring system for oral feeding of premature infants was proposed to monitor the sucking–swallowing–respiratory activities and the heart rate variability to provide quantitative indices of oral feeding. Here, a novel sucking pressure sensing module was also developed to monitor the premature infant’s sucking pressure under oral feeding to avoid the immersion influence of milk. The experimental results showed that the proposed system detected the related physiological parameters of premature infants during oral feeding effectively and may provide an objective clinical evaluation tool for oral feeding ability and safety of premature infants in the future.