The modulatory effect of different concentrations of ethanol extract of matured leaves of M. esculenta, Crantz at 200, 600, 1000 and 1400 µg/ml was investigated in vitro on mitochondrial membrane permeability transition pore in liver, kidney and heart of diabetic animals in the absence and presence of 20 µM exogenous Ca2+. The extract at these concentrations had no significant (p< 0.05) effect on mitochondrial membrane permeability transition (MPT) pore of the three organs in the absence of Ca2+. However, in the presence of Ca2+, the extract exhibited significant (p< 0.05) inhibition of mitochondrial membrane transition pore opening: liver by 62.66%, 42.47%, 22.44% and 17.63% at 1400, 1000, 600, and 200 µg/ml, respectively. In the heart, inhibition of MMPT pore opening was by 92.86%, 71.43%, 64.29% and 57.14% at 200, 600, 1400, and 1000 µg/ml, respectively. In the kidney, the extract also inhibited mitochondrial membrane transition pore opening in a concentration-dependent manner by 92.65%, 91.18%, 89.71% and 72.06% at 1400, 1000, 600, and 200 µg/ml, respectively. Caspase-3 activity in vitro was also reduced with increasing extract concentrations; thus confirming that the extract inhibits MMPT pore opening in the presence of Ca2+. The extract may be able to protect these organs against damage, resulting from Ca2+ overload that may trigger cell death, and as such it may be useful in the management of diseases related to tissue wastage such as cardiomyopathy and nephropathy which are associated with Type 2 diabetes mellitus.