Problems in healthcare and medicine are worldwide and multifaceted. This dissertation explores optimal and efficient designs in global and other important clinical trials with nature-inspired metaheuristic algorithms. The primary objective of this research is to showcase novel uses of metaheuristics in two real world applications: first, we collaborate with physicians and help patients with bipolar disorder by designing optimal sampling times for sustained-release lithium, a vital medication using pharmacokinetics/pharmacodynamics nonlinear mixed effects models and second, to optimize worldwide clinical trial patient recruitment plans within tight, real world complex regulatory and budgetary constraints. We determine interesting optimal designs using metaheuristics in both single and multiple objective situations with complex constraints. We show systematic analyses which can be used to solve and enhance the implementation and interpretability of the discussed real life clinical trial designs. The results from this dissertation are implemented in current software and offer novel insights into the design of experiments and patient recruitment strategies, contributing to the advancement of medical treatments and healthcare practices.