Oil-in-water (O/W) and water-in-oil (W/O) MEEKC were compared for their abilities to separate and detect eight phenolic acids and five diterpenoids in Radix et Rhizoma Salviae Miltiorrhizae (RRSM). The effects of oil type and concentration, organic modifier, SDS, and buffer concentration on separation were examined in order to optimize the two methods. Oil contents and organic modifier were found to markedly influence the separation selectivity for both O/W and W/O systems. SDS concentration rarely affected separation resolution for O/W MEEKC, and separation of eight phenolic acids and five diterpenoids could be improved by changing the buffer concentration for W/O MEEKC. A highly efficient O/W MEEKC separation method, where the 13 compounds were separated with baseline resolution, was achieved by using a microemulsion solution of pH 8.0 containing 0.6% cyclohexane, 3.0% SDS, 6.0% 1-butanol, and 3.0% ACN. The W/O MEEKC was unable to resolve all the components. In addition, the analytic time in O/W MEEKC was shorter than that in W/O MEEKC. Finally, the developed O/W MEEKC method was successfully applied to determine analytic compounds in RRSM samples.