The aim of this study was to investigate the effect of a senior-friendly diet based on the dietary inflammatory index (DII) on the nutritional status and health indicators of older people. A total of 256 participants were classified into tertiles based on their DII values and split into intervention (n = 201) and control (n = 55) groups. The intervention group was provided with a senior-friendly diet, and the control group was allowed to eat their usual diet. Before and after the trial, anthropometric measurements, blood analyses, and questionnaires were completed for both groups. The mean age of the participants was 82.49 years, and 66.4% were female. On average, participants had 2.5 medical conditions, with a notable prevalence of cardiovascular disease. Following the intervention, the energy, carbohydrate, protein, and fat intakes significantly increased in the intervention group compared to pre-intervention levels. Tertile 3 exhibited substantial improvements in total nutrition score, NQ-E balance, and DII total score, as well as in triglycerides and blood glucose, attributed to this dietary intervention compared to other groups. In comparison with Tertile 1, nutrient intake and nutritional status in Tertile 3 were closely associated with significant influencing factors of the dietary intervention. For the group with the worst DII (Tertile 3), this dietary intervention greatly improved nutritional status, nutrient intake, and clinical indicators; thus, this senior-friendly diet appears to be beneficial for elderly people with nutritional vulnerabilities.