This aim of this study is to prepare four novel oil-in-water creams from 100% naturally sourced oil ingredients such as jojoba, baobab and coconut oil, and compare the effect of the oils on the physico-chemical properties of the creams and their short- and long-term stability. Four 100 g each oil-in-water active containing creams and their controls (without the active ingredient) were formulated and stored in eight separate glass jars. The short-term stability of the creams was assessed via phase separation resistance, pH, microscopic size analysis, globule size, zeta potential, conductivity and microbial challenge evaluation after 8, 14 and 28 days, under three different storage temperature conditions (4 °C, 25 °C and 40 °C) and at ambient relative humidity. Model creams IA, IB, IIA, and IIB containing 1:1 of jojoba and baobab oil mix, all had good shelf-life or stability at the end of the 28 days after storage at 4 °C, 25 °C and 40 °C, compared to models IIIA, IVA and pairs. The long-term stability of creams stored at 25 °C for 28 days, was subsequently assessed using the Dynamic Vapor Sorption system. Model creams IB, IIB, IA and IIA showed the lowest percentage moisture loss or change in mass during a period of desorption steps. Therefore, the creams containing a mixture of jojoba and baobab oils are capable of retaining moisture easily for an extended period of time when compared to the creams containing jojoba and coconut oil or baobab and coconut oil combinations, thus they were proven to be the best products in terms of stability and quality. The stability ranking of the creams using the novel DVS method was in congruence with the results from the short-term stability experiments. This novel DVS method can, therefore, be generically applied in the cosmetic, food and pharmaceutical industries for the evaluation of the long-term stability of semisolids.