Diabetic cardiomyopathy is associated with metabolic changes including decreased glucose oxidation (Gox) and increased fatty acid oxidation (FAox), which result in cardiac energetic deficiency. Diabetic hyperglycemia is a pathophysiological mechanism that triggers multiple maladaptive phenomena. The mitochondrial calcium uniporter (MCU) is the channel responsible for Ca²⁺ uptake in mitochondria and free mitochondrial calcium concentration ([Ca²⁺]m) regulates mitochondrial metabolism. Experiments with cardiac myocytes (CM) exposed to simulated hyperglycemia revealed both reduced [Ca²⁺]m and MCU protein levels. Therefore, we investigated whether returning [Ca²⁺]m to normal levels in CM by expressing MCU could lead to normalization of Gox and FAox with no detrimental effects. Mouse neonatal CM were exposed for 72 h to either normal glucose (5.5 mM glucose plus 19.5 mM manitol, NG), high glucose (25 mM glucose, HG), or HG plus adenoviral MCU expression. Gox and FAox, [Ca²⁺]m, MCU levels, pyruvate dehydrogenase activity (PDH), oxidative stress, mitochondrial membrane potential (m) and apoptosis were assessed. Results showed that [Ca²⁺]m and MCU protein levels were reduced after 72h of HG. Gox was decreased and FAox was increased in HG along with decreased PDH activity, higher phosphorylated PDH levels and reduced m. MCU expression returned these parameters towards NG levels. Moreover, increased oxidative stress and apoptosis were reduced in HG by MCU expression. Relevantly, we also observed reduced MCU protein levels and [Ca²⁺]m in hearts from type 1 diabetic mice. Thus, we conclude that HG-induced metabolic alterations can be reverted by restoring MCU levels resulting in return of [Ca²⁺]m to normal.