Indicator papers based on immobilized reagents with their subsequent digital image processing are widely used for the quick and cheap screening study of drugs when assessing the content of the main substance in drugs for the presence of counterfeits. Indicator papers based on reagents immobilized on a cellulose matrix 4-dimethylaminocinnamic aldehyde (DMACA), 4-dimethylaminobenzaldehyde (DMAB), and 3-methoxy-4-hydroxybenzaldehyde (vanillin) were proposed for the determination of β-lactam antibiotic cefotaxime. To specify optimal conditions for the immobilization of reagents on a solid matrix, the intensities (changes in intensities) of color parameters were recorded at a different concentration of reagents, type of surfactants, and paper porosity. The detection limits of visual-colorimetric determination of cefotaxime were 1.0 mg/ml (DMACA), 0.12 mg/ml (DMAB), and 0.30 mg/ml (vanillin). Colorimetric processing of images of the test agents was carried out in the GIMP (GNU Image Manipulation Program) 2.10 program by averaging the images of indicator papers using the blur-sharp function, determining the intensity of color parameters. The photos were taken using a 48-megapixel camera of a POCO X3 pro smartphone in a specialized box measuring 22 × 23 × 24 cm with two LED lighting strips (5 V, 1 A). Linear dependences of the intensities of color parameters of the RGB, HSV, and CMYK models on the cefotaxime concentration (log c) were obtained: y = –15x + 45 (r2 = 0. 99, color parameter H for DMACA), y = –51x + 130 (r2 = = 0.99, parameter B for DMAB), y = 36x + 30 (r2 = 0. 99, S parameter for vanillin). Linear dependences of the areas and perimeters of the petal diagrams of indicator papers on the cefotaxime concentration have been plotted for the studied systems of cefotaxime — immobilized reagent. The correctness of the determination results was assessed using the analysis of spiked samples, the relative error did not exceed 25%. The developed test tools based on immobilized aromatic aldehydes are recommended for the semi-quantitative determination of cefotaxime.