In this study, hydrothermal co-liquefaction of restaurant waste for biocrude production was conducted. The feedstock was resembled using the organic fraction of restaurant waste and low-density polyethylene, polypropylene, polystyrene, and polyethylene terephthalate, four plastic types commonly present in municipal solid waste. Using design of experiment and a face-centered central composite design, three factors (feedstock plastic fraction, temperature, time) were varied at three levels each: feedstock plastic fraction (0, 0.25, 0.5), temperature (290 °C, 330 °C, 370 °C), and reaction time (0 min, 30 min, 60 min). The literature reports positive synergistic interactions in hydrothermal co-liquefaction of biomass and plastics; however, in this work, only negative synergistic interactions could be observed. A reason could be the high thermal stability of produced fatty acids that give little room for interactions with plastics. At the same time, mass might transfer to other product phases.