A simple and rapid analytical procedure for determination of saccharin (SAC) and acesulfame-K (AC-K) based on UV-vis measurements and partial least squares (PLS) was proposed. Thus, an experimental design at levels 2 and 15 mg l−1 for SAC and 2 and 20 mg l−1 for AC-K was applied. Because real samples usually contain SAC and AC-K combined with aspartame (ASP), this interference was also included in the model. The procedure was successfully applied for SAC and AC-K simultaneous determination in sweeteners and fruit juice powders, without any separation step to remove ASP. The results were validated by using spiked samples, and the obtained recoveries were satisfactory.