Holistic sidewall ventilation system (HSVS) is characterized by uniform temperature distribution in the poultry house. Yet two challenges remain: low air velocity at the front cross-section and suboptimal positions of recirculation zones in large-scale facilities. The airflow field is governed by the configuration and regulation of air inlets. In this study, the airflow distribution was optimized to enhance overall ventilation performance in HSVS poultry houses. The opening angles of local front inlets were also adjusted using field measurements and numerical simulations. A systematic analysis was implemented to explore the effects of inlet angles on the airflow field. A full-scale HSVS poultry house was selected as the research object, where 118 sidewall air inlets were divided into front, middle, and rear segments (40, 40, and 38 inlets, respectively). Two ventilation scenarios (with 3 and 4 operational fans) were evaluated, wherein the opening angles of the front inlets were adjusted within the range of 10° to 90°, whereas the middle and rear air inlets were kept at fixed angles to match the ventilation scenarios. Air velocity and pressure difference were continuously measured at 6 sensor points in the laying hen activity zone (1.5 m above the ground). Computational fluid dynamics (CFD) incorporated with the Reynolds-averaged Navier-Stokes (RNG) k-ε turbulence model was adopted to simulate the airflow field. The air velocity non-uniformity coefficient was employed as the evaluation metric to quantify the uniformity of airflow distribution. The results showed that different ventilation scenarios displayed an identical variation trend. The opening angle of the front air inlets reduced the static pressure difference between the inlets and the outdoors, while preserving a uniform distribution of pressure difference. The average pressure difference in the middle section of the poultry house was higher than that at the front end, with an average difference of (1.7±0.2) Pa. This discrepancy was also independent of both the inlet opening angle and the ventilation scenario. Meanwhile, air velocity increased with an increase in the opening angle of the front air inlets, indicating a negative correlation with pressure difference. Under the scenario with 3 operational fans, the maximum average air velocity in the front and middle segments reached (0.18±0.02) m/s (at 70°) and (0.30±0.06) m/s (at 90°), respectively; Under the scenario with 4 operational fans, these values were (0.25±0.04) m/s (at 90°) and (0.38±0.06) m/s (at 90°), respectively. Furthermore, the front inlet opening angle was adjusted to alleviate inadequate ventilation in the front section of the house, indicating a moderate improvement in air velocity in the middle section. The air velocity non-uniformity coefficient decreased consistently, as the inlet angle increased, thus dropping to below 0.30 at the angle of 70° or larger (0.24 for 3 fans and 0.30 for 4 fans at 70°). Subsequently, two optimal operating conditions were selected for further CFD simulation analysis. CFD simulation results showed that the front inlet angles enhanced the overall indoor air velocity, where the average air velocity at the front cross-section increased by 0.10 m/s. The optimal inlet angles effectively mitigated front ventilation dead zones for the airflow uniformity, indicating less unfavorable recirculation zones. The opening angle of the front air inlets was adjusted to 70° or larger for the weak ventilation zone at the front of HSVS poultry houses, indicating indoor airflow uniformity. Zoning regulation of air inlet angles can offer a cost-effective and efficient solution to enhance the ventilation performance of HSVS poultry houses. The finding can provide the theoretical basis and technical support for environmental control optimization in large-scale poultry houses. Future research can be expected to integrate the heat and mass exchange between hens and the environment in smart agriculture.