The kidney contains numerous mitochondria in proximal tubular cells that provide energy for tubular secretion and reabsorption. Mitochondrial injury and consequent excessive reactive oxygen species (ROS) production can cause tubular damage and play a major role in the pathogenesis of kidney diseases, including diabetic nephropathy. Accordingly, bioactive compounds that protect the renal tubular mitochondria from ROS are desirable. Here, we aimed to report 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), isolated from the Pacific oyster (Crassostrea gigas) as a potentially useful compound. In human renal tubular HK-2 cells, DHMBA significantly mitigated the cytotoxicity induced by the ROS inducer L-buthionine-(S, R)-sulfoximine (BSO). DHMBA reduced the mitochondrial ROS production and subsequently regulated mitochondrial homeostasis, including mitochondrial biogenesis, fusion/fission balance, and mitophagy; DHMBA also enhanced mitochondrial respiration in BSO-treated cells. These findings highlight the potential of DHMBA to protect renal tubular mitochondrial function against oxidative stress.