: MicroRNAs (miRNAs) have emerged as molecular mediators involved in the pathogenesis of rheumatoid arthritis (RA). Given the influence of diet on gene expression and inflammation, plant-based diets represent a potential non-pharmacological strategy for modulating disease activity. This study aimed to explore and validate, through a bioinformatic-guided pilot approach, the regulation of miRNAs associated with RA in response to a 14-day plant-based dietary intervention. : Candidate miRNAs were identified through differential expression analysis of the GSE124373 dataset using GEO2R and were further supported by a literature review. Target gene prediction and functional enrichment analyses were conducted to assess the biological relevance of these findings. Twenty-three RA patients followed a plant-based diet for 14 days. The clinical activity (DAS28-CRP), biochemical markers, and plasma expression of five selected miRNAs (miR-26a-5p, miR-125a-5p, miR-125b-5p, miR-146a-5p, and miR-155-5p) were evaluated before and after the intervention using RT-qPCR. : Significant reductions were observed in DAS28-CRP scores, C-reactive protein, glucose, and lipid levels after 14 days of intervention. Three of the five miRNAs (miR-26a-5p, miR-125a-5p, and miR-155-5p) were significantly downregulated post-intervention. Bioinformatic analyses indicated that these miRNAs regulate immune-inflammatory pathways relevant to RA pathogenesis. : This pilot study suggests that a short-term plant-based dietary intervention may modulate circulating miRNAs and improve clinical and biochemical parameters in RA patients. These findings support further research into dietary strategies as complementary approaches for RA management.