Nurse-led sedation (NLS) protocols and structured delirium screening improve outcomes in mechanically ventilated adults by standardizing targets for light sedation and enabling early detection of delirium. We systematically synthesized original studies evaluating (1) NLS/protocol-directed sedation and (2) bedside delirium screening using CAM-ICU or ICDSC in ventilated ICU patients. Nine primary studies met criteria: two randomized/controlled comparisons of sedation strategies and seven observational before-after or implementation studies. Across studies, NLS protocols commonly reduced sedative exposure and, in several cohorts, shortened ventilation or improved ventilator-free days, with neutral effects on safety. A nurse-implemented protocol lowered ventilator-associated pneumonia from 15% to 6% and halved median ventilation duration (8 to 4.2 days). In an RCT, a nurse-implemented algorithm outperformed daily sedation interruption, with shorter ventilation and faster organ-failure recovery. For delirium screening, implementation of CAM-ICU/ICDSC improved nurses’ diagnostic performance and agreement with reference assessors, while large-scale implementation showed feasibility without adverse effects on length of stay. Overall, NLS protocols and routine CAM-ICU/ICDSC screening appear safe and practicable and are associated with reduced ventilation time and improved process outcomes, while effects on delirium incidence and mortality are heterogeneous. These findings align with guideline targets for light sedation and routine delirium monitoring.