To examine mitochondrial dysfunction as a key driver of diabetic kidney disease (DKD) and to evaluate the Mediterranean diet (MD) as a potential nutritional modulator of renal mitochondrial health.

Clinical, epidemiological, and preclinical studies addressing mitochondrial alterations in podocytes and proximal tubular cells were critically reviewed, with particular attention to MD adherence and MD-derived bioactive compounds.

Evidence indicates that early, cell-specific mitochondrial dysfunction contributes to DKD progression through impaired bioenergetics, oxidative stress, altered mitochondrial dynamics, defective mitophagy, and reduced biogenesis. Clinical and epidemiological studies consistently associate higher MD adherence with preserved renal function and lower DKD risk, while experimental studies suggest that MD-derived bioactives modulate mitochondrial quality control pathways in renal cells.

The MD–mitochondria axis represents a biologically plausible framework linking nutrition and mitochondrial homeostasis in DKD. Mediterranean diet adherence may therefore contribute to renal resilience and complement current strategies aimed at preventing DKD progression.