Four simple, sensitive, economical, and eco-friendly spectrophotometric and spectrofluorimetric methods for the assay of erdosteine (ERD) in bulk and dosage form have been developed and validated as per the current ICH guidelines. Method I involved the addition of the powerful oxidizing agent, potassium permanganate to ERD and measuring the oxidation product at 600 nm. Another oxidizing agent; ceric ammonium sulfate was used in Method II where ERD is oxidized resulting in a decline in the absorbance intensity of cerium (IV) ions, measured at 320 nm. Similarly, Method III employed the use of ceric ammonium sulfate, However, the fluorescence intensity of the resulting cerium (III) ions was recorded at λex/λem 255/355 nm, respectively. Whereas in Method IV, ERD was added to acriflavine leading to a proportional decrease in its native fluorescence. Various reaction conditions affecting the intensity of measurement were attentively investigated, optimized, and validated. All the suggested methods did not require any tedious extraction procedures nor organic solvents. The implementation of the proposed methods in ERD assay resulted in linear relationships between the measured signals and the corresponding concentrations of ERD in the range of 1–6, 0.1–1.0, 0.01–0.1, and 10–100 μg/mL with LOD values 0.179, 0.024, 0.0027 and, 3.2 μg/mL for methods I, II, III and IV respectively. The suggested methods were successfully applied to ERD analysis in pure form and in commercial capsules. Furthermore, the eco-friendliness of the proposed methods was thoroughly checked using various greenness testing tools. Lastly, this work, not only presents highly sensitive, green, mix-and-read methods for ERD determination, but also, describes the determination of ERD spectrofluorimetrically for the first time in the literature.