Gentamicin (GM), a broad-spectrum aminoglycoside antibiotic has insignificant small intestinal absorption and this makes its oral administration impracticable. Its orally administrable product in addition to parenteral delivery formula is necessary. In this study in vitro evaluation of the stability of a self-micro-emulsifying drug delivery systems (SMEDDS) prepared with varying ratios of softisan ® 154 (S-154) and precirol ® ATO 5 (P-5) and loaded with GM was carried out. Batches of SMEDDS were prepared as: A1, S-154/P-5(1:1), A2, S-154/P-5(1:1), A3, S-154/P-5(1:1), A4, S-154/P-5(1:1) loaded with 50, 100, 200 and 0 mg of GM respectively. Similarly batches B1,S-154/P-5(1:2), B2,S-154/P-5(1:2), B3,S-154/P-5(1:2), B4,S-154/P-5(1:2) and C1,S-154/P-5(2:1), C2,S-154/P-5(2:1), C3,S-154/P-5(2:1), C4,S-154/P-5(2:1) were prepared. The micro-particles yield, time dependent particle size, pH, thermal analysis, encapsulation efficiency and in vitro antimicrobial efficacy of the SMEDDS were investigated. Batch B3, S-154/P-5(1:2) gave the highest yield of micro-particles while those of B1, S-154/P-5(1:2) and C2, S-154/P-5(2:1) respectively were the most stable. Between 7 and 60 days, B1, S-154/P-5 (1:2), B2, S-154/P-5 (1:2), B3, S-154/P-5 (1:2), C1, S-154/P-5 (2:1) and C2, S-154/P-5 (2:1) were stable in their pH. Batch B3, S-154/P-5 (1:2) presented with higher encapsulation efficiency as well as thermostability. The highest inhibition zone diameter (IZD) of 14 mm was obtained with C3, S-154/P-5(2:1). This compared to A3, S-154/P-5(1:1) and B3, S-154/P-5(1:2) with IZDs of 9 and 12 mm respectively. The formulations containing softisan and precirol in the ratio of 1:2 and 2:1 respectively were most stable in pH, particle size and thermostability and may likely be useful for oral administration.