Our study aimed to assess the effects of creating a healing environment and clustering nursing care on premature infants’ vital signs, pain, and sleeping. The study had an experimental research design for the control and study group, each with 53 premature infants. We collected the data through the Vital Signs Sheet, Premature Infant Pain Profile, and Neonatal behavioral state. We used T-tests and chi-square tests to assess the differences between groups. There was a highly statistically significant difference between the study and control groups concerning respiration (p-value<0.01) and heart rate, systolic blood pressure, and O² saturation (p-value<0.05). 90.6% of participants in the study group had a mild total premature infant pain profile, while 37.7% of the control group had a moderate total premature infant pain profile score. Applying a healing environment and clustering nursing care significantly improved respiration, heart rate, oxygen saturation, and systolic blood pressure. Furthermore, it increased sleep time and decreased wake state and pain score.