The presence of pharmaceutical compounds has been increasingly frequent in aquatic matrices. This is due to the low efficiency of treatment plants against these compounds. Therefore, in this work, the efficiency of the treatment via heterogeneous photo-Fenton process was studied, containing a mixture of the drugs atenolol and propranolol, in two matrices (aqueous solution (AS) and synthetic effluent (SE)), using magnetite as catalyst. Univariate studies to verify the influence of the operational parameters have shown that it is possible to treat contaminants at the natural pH of the solution (5–6), which is not possible when dealing with homogeneous Fenton reactions. It was also observed that [magnetite] equal to 3.5 g‧L−1 and [H2O2] of 80 mg‧L−1 are efficient to promote the degradation of drugs in AS, reaching 94.8 and 100% for the groups analyzed at wavelengths of 215 and 280 nm, respectively. For the SE the results obtained were equal to 41.8 and 97.3% at λ of 209 and 280 nm. The drug degradation kinetics, in the two matrices, showed a pseudo-first-order profile, with no formation of by-products after chromatographic analysis. With this, it was evidenced that the treated matrices did not present toxicity to the seeds.