Both photocatalytic and enzymatic degradation of phenol were studied in order to evaluate and to compare the catalytic potential of both methods. For this, solar-sensitive ZnMe (Me = Al, Cr) layered double hydroxides (LDHs) and their derived mixtures of mixed oxides (MMOs) were synthesized via co-precipitation and calcination at 750 °C, while the calcined LDH at 550 °C was used for horseradish peroxidase (HRP) immobilization through absorption. The structural, optical and thermal properties of catalysts were investigated by XRD, FTIR, TG/DTA, TEM and UV–Vis analyses. We approached here for the first time the use of LDH–HRP biohybrid for phenol degradation. Further, since HRP operates similarly as photocatalysts, we also investigated the ability of LDH–HRP to generate photo-enzymatic responses, when the biocatalyst is used under solar light. Both degradation methods are able to remove phenol from solution via different pathways, namely step-by-step phenol photodegradation and phenol enzymatic polymerization, when an insoluble product is obtained at the end of reaction. After 7 h of reaction, 95% of phenol was removed by a MMOs, while ZnAlLDH + light, ZnAlLDH–HRP and ZnAlLDH–HRP + light removed 20, 25 and 35% of phenol via photo-, enzymatic and photo-enzymatic catalysis, respectively.