Constituents of liquid smoke possess a huge potential to be converted as value-added chemicals, such as flavoring, antiseptics, antioxidants, or even fossil oil substitutes. However, liquid smoke instability, led by the presence of oxygenate compounds, is an obstacle for further utilization and processing. On the other hand, catalyst efficiency in hydrodeoxygenation (HDO) remains challenging. Sarulla natural zeolite (Z), with abundant availability, has not been comprehensively investigated in the catalytic performance of HDO. In this study, Sarulla natural zeolite with different Si/Al ratios, which are activated by several concentrations of hydrochloric acid and nickel supported by Z (Ni-Z) synthesized by wet impregnation, were evaluated for HDO of liquid smoke, particularly in reducing oxygenate compounds. Catalyst morphology, surface area, pores, and crystallinity are investigated. Catalytic performances were evaluated, particularly on reducing oxygenate compounds and the shifting of phenol and its derivatives. Furthermore, the liquid smoke product of HDO was analyzed by gas chromatography-mass spectrometry (GC-MS). The data obtained reveal that the HDO process of liquid smoke with the Z3 catalyst shows the best activity compared to Z5 and Z7, with phenol conversion of 62.39% and 11.93% of alkoxy reduction. Meanwhile, the best Ni metal catalyst system activity was given by the Ni-Z5 catalyst compared to Ni-Z3 and Ni-Z7, where phenol conversion and alkoxy reduction were at 60.06% and 11.49%, respectively.