Objective This study aimed to investigate the effects and underlying mechanisms of Lonicera japonica in delaying renal aging. Methods A mouse model of renal aging was established via intraperitoneal injection of D-galactose (D-gal), with concurrent administration of Lonicera japonica decoction by oral gavage. Following behavioral assessments, kidney tissues were collected from each group for enzyme-linked immunosorbent assay (ELISA) and senescence-associated β-galactosidase (SA-β-gal) staining to evaluate model induction and the protective effects of Lonicera japonica. Subsequently, integrated miRNA transcriptomic and proteomic sequencing analyses were conducted to identify statistically significant differentially expressed miRNAs (DEMs) and proteins (DEPs). Functional annotation and pathway enrichment of these DEMs and DEPs were performed using GO and KEGG databases. Results Behavioral tests, including the Morris water maze and forced swimming test, revealed that model mice exhibited significant impairments in learning, memory, and exercise endurance compared to controls (P<0.05). Lonicera japonica treatment markedly ameliorated these aging-related deficits (P<0.05). ELISA and SA-β-gal staining DEMsonstrated that renal IL-6 levels and the percentage of SA-β-gal-positive area were significantly elevated in the model group relative to the control group (P<0.001), both of which were substantially reduced following Lonicera japonica intervention (P<0.01). Integrated omics analysis identified 11 significant DEMs and 8 significant DEPs. Intersection analysis of target genes revealed miR-146b-3p/Tmprss13 as a key regulatory pair, while miR-150-3p/Brpf1 and miR-1934-5p/Cln8 were identified as two miRNA-protein pairs concurrently downregulated by Lonicera japonica. GO and KEGG enrichment analyses indicated that Lonicera japonica may delay renal aging by activating LjREcsit (Lonicera japonica-regulated Ecsit), a differentially expressed gene involved in the MAPK signaling pathway. Conclusion Lonicera japonica effectively attenuates D-gal-induced renal aging in mice. The underlying mechanisms may involve inhibition of miR-146b-3p leading to activation of Tmprss13, or coordinated downregulation of miR-150-3p/Brpf1 and miR-1934-5p/Cln8. Additionally, modulation of the MAPK signaling pathway via LjREcsit represents a critical mechanism through which Lonicera japonica exerts its renoprotective and anti-aging effects.