AbstractPalladium nanohybrids were synthesized and applied to the one‐pot synthesis of bis(3‐indolyl)methanes by selective C−C bond reaction from benzyl alcohol and indole. A T. lanuginosus lipase‐palladium nanoparticles hybrid (Pd@TLL) was synthesized, yielding PdNPs with an average diameter size of 5 nm. This heterogeneous catalyst was first tested in the selective oxidation of benzyl alcohol to benzaldehyde in different solvents. Then, the direct formation of bis(3‐indolyl)methane, by in situ oxidation and C−C coupling, was successfully evaluated under different conditions, obtaining >99 % conversion at 80 °C in toluene, with a TOF value of 9 min−1 and 89 % in pure water, demonstrating the versatility of these biohybrids.