© 2021 International Society for Hemodialysis.Introduction: Protein energy wasting/malnutrition is a strong predictor of morbidity and mortality in patients on maintenance hemodialysis (MHD). We aimed to compare the effects of oral and/or intradialytic parenteral nutrition (IDPN) support on nutritional and inflammatory parameters in malnourished patients with MHD. Methods: This is an observational study of 56 malnourished patients on MHD. We offered combined oral nutritional support (ONS) and IDPN for 12 months to all patients. Depending on patient choices for treatment, they were classified into four groups: group 1 (ONS only), group 2 (IDPN only), group 3 (both ONS and IDPN), and group 4 (patients who refused artificial nutrition support and only followed dietary advice). Normalized protein catabolic rate (nPCR), malnutrition inflammation score (MIS), and body composition (fat mass [FM], muscle mass [MM]) were assessed monthly. Findings: The mean serum albumin levels of groups 2 and 3 significantly increased with the intervention, whereas that of group 4 significantly decreased. The mean nPCR levels of groups 2 and 3 significantly increased. Group 3 had the most significant positive change in serum albumin and nPCR levels. Mean serum C-reactive protein (CRP) levels of groups 1, 2, and 3 decreased, whereas those of group 4 increased. A ∆ in CRP was only identified in group 3. The MIS of groups 1, 2, and 3 significantly decreased whereas that of group 4 significantly increased. The ∆% in FM was 1.1, 1.9, 9.1, and −2.9 for groups 1, 2, 3, and 4, respectively, and that in MM was −0.6, 4.4, 6.9, and −7.9 for groups 1, 2, 3, and 4, respectively. Discussion: Compared to monotherapy or nutritional counseling, the choice of ONS plus IDPN is associated with improved nutritional status and decreased inflammation in malnourished patients on MHD. Nonetheless, interventional studies must be conducted to confirm these observations.