<p>In this work, we present a new approach to assessment of possible harmful effects of popular chemical reactions on living organisms by means of the Build-a-bio-Strip platform. This approach allows direct comparisons of different synthetic routes to a particular chemical product from the viewpoint of reaction cytotoxicity potentials. Here it was used to compare widespread palladium- and copper-based catalytic systems, as well as photocatalytic systems, utilized in synthesis of four compounds—diphenylamine, 4-phenylmorpholine, 1-phenylpiperidine, and <i>N</i>-phenylnaphthalen-1-amine—via four types of reactions (Buchwald-Hartwig reactions, Ullman-Goldberg reactions, Chan-Lam reactions, and photocatalytic reactions). According to the results, the safest synthetic routes were the Buchwald-Hartwig reactions that utilized Pd(OAc)₂ or PdCl₂ as catalyst. Notably, the studied Pd-based catalytic systems outperformed the Cu-based ones in terms of their contribution to the “total cytotoxicity” of chemical reactions both because of their lower loadings and cytotoxicity that was comparable or lower than the cytotoxicity of the tested copper compounds.</p> Graphical Abstract <p></p>