The present study was dedicated for solving the challenge of the overlapped spectra of olanzapine (OLZ) and fluoxetine (FLX) for their concurrent, accurate and precise determination without prior physical separation. The developed methods had to venture away from those that depend on chromatography, because of their negative effects on the environment due to using hazardous organic solvents as well as their high cost. The suggested methods were based on spectrophotometry combined with simple mathematical treatments of the spectra. These approaches are simple, rapid, inexpensive and reliable options for the effective assay of FLX and OLZ in pharmaceutical dosage forms. Ratio subtraction method was devoted for estimation of both drugs, while dual wavelength method and absorptivity factor method could be utilized in the estimation of FLX and OLZ, respectively. All the suggested methods were efficiently applied for the determination of the studied drugs in laboratory prepared mixtures and their pharmaceutical formulations. The environmental safety of the involved procedures was assessed by applying the Eco Score scale and complex modified GAPI methods. The methods were proved to be highly safe since no large volume of solvents were used, and no derivatizing reagent or drastic experimental conditions were involved. In addition, the procedures consume little energy and produce a small amount of waste. In conclusion, for FLX determination, the use of dual wavelength method is preferable because it needs very low mathematical treatment than the ratio subtraction method. However, for OLZ, the ratio subtraction method has higher sensitivity than absorptivity factor method although the latter is simpler.