High-quality indoor air is essential in open-kitchen restaurants for ensuring a healthy workplace and comfortable conditions for visitors. In this study, indoor air quality interdependence between the kitchen and the dining zones in open-kitchen restaurants was analyzed. The method was based on measurements of selected air parameters using a sensor technique and mutual information (MI) analysis. A long-term approach (based on a several-hour time series) and a short-term approach (based on a several-minute time series) were applied. This study involved four open-kitchen restaurants. The indoor conditions were represented by the temperature, relative humidity, CO2 concentration, and content of the total volatile organic compounds (TVOC) in the air. The MI analyses showed that the long-term co-dependence of the indoor conditions between the kitchen and the dining zones was smaller during business hours (MI = 0.12 ÷ 0.40) compared to night hours (MI = 0.24 ÷ 0.58). The ranking of the long-term MI values for the individual air parameters was MICO2 (0.34) ≅ MIT (0.34) > MIRH (0.28) > MITVOC (0.23). The short-term interdependencies were smaller during night hours (median MI = 0.01 ÷ 0.56) compared to business hours (MI = 0.23 ÷ 0.61). Additionally, the short-term MI was subject to high temporal variability. The ranking of the short-term MI values for the individual air parameters was MICO2 (0.48) > MIT (0.46) > MIRH (0.37) > MITVOC (0.26). Due to the weak and highly variable co-dependence of the air parameters between the kitchen and dining areas, multi-zone monitoring of air parameters with an emphasis on TVOC measurements is recommended to ensure proper indoor conditions in open-kitchen restaurants. The presented approach may be applied to design indoor air quality monitoring and ventilation systems not only in open-kitchen restaurants but also in other interiors with functionally different zones.