Feeding problems are common in premature infants (PIs) and may lead to negative consequences such as malnutrition, dehydration, excessive weight loss, as well as developmental and psychological deficits. Moreover, they are associated with increased length of hospital stay/cost. There is not enough evidence on how feeding problems should be treated in PIs. The goal of this study was to investigate the effects of non-nutritive sucking combined with oral motor stimulation and oral support on feeding performance in PIs. A single-blind randomized clinical trial was performed on 44 PIs with feeding problems. Patients were randomly categorized into two groups: (1) combined intervention (CI) and (2) non-nutritive sucking (NNS). The CI group received NNS, oral motor stimulation and oral support simultaneously. Infants in both groups received 14 treatment sessions for 14 consecutive days. The Preterm Oral Feeding Readiness Assessment Scale (POFRAS) was used as the primary outcome measure. Weight, volume of milk intake, time to achieve full oral feeding, and length of hospital stay were secondary outcome measures. All measures were assessed before treatment, after the 7th session, after the 14th session, and after 7 days after the end of treatment. Both groups improved in all outcome measures across time (P < 0.001). The improvements in the POFRAS, volume of milk intake, and time to achieve full oral feeding were significantly greater in the CI group than the NNS group (P < 0.001). The improvements attained in weight and length of hospital stay were not significantly different between the CI and NNS groups (P > 0.05). Large effect sizes were found for POFRAS score in both CI (d = 3.98) and NNS (d = 2.19) groups. The current study showed that the combined intervention including NNS, oral motor stimulation, and oral support significantly improved the feeding performance in PIs.