Sodium is an essential component of the human body, with known influences on obesity. This paper reports the effect of cube natural sea salt (CNS) on the reduction of obesity in high fat diet-induced obese C57BL/6 mice and 3T3-L1 adipocytes, by ameliorating the obesity parameters and obesity-related gene mechanisms. The suppression of high fat diet-induced obesity and differentiated 3T3-L1 adipocytes by sea salt depends on the manufacturing process and mineral content. The manufacturing method using only new sea water (Cube natural sea salt) decreases the magnesium (Mg) and sulfur (S) content in the salt with different crystallization and morphologies, compared to the general manufacturing method (Generally manufactured sea salt, GS). Mg in salt is known to considerably affect obesity; an appropriate concentration of magnesium chloride (MgCl2) reduces lipid accumulation significantly and regulates the lipogenesis and liver enzyme activity. Our results indicate that sea salt contains an appropriate level of Mg as compared to table salt (purified salt, NaCl), and is important for regulating obesity, as observed in the in vivo and in vitro anti-obesity effects of CNS. The Mg content and mineral ratio of sea salt are important factors that ameliorate the lipid metabolism and liver enzyme activity in high fat diet induced obesity, and contents of Mg in sea salt can be altered by modifying the manufacturing process.