Consumer preferences, safety, and sustainability aspects of conventional cosmetic ingredients have contributed to an increase in the demand for natural cosmetic ingredients and products. Naturally derived active cosmetic agents and excipients may come into contact with various naturally occurring and synthetic contaminants throughout the supply chain, and substantiating their safety is essential. This review examines the safety and legislative requirements applicable to natural cosmetic ingredients in the European Union (EU). Cosmetic safety requirements include technical data based on the ingredient profile, presence of hazards and the risks associated with the intended conditions of use. The hazard analysis includes screening for microbial contaminants such as aerobic mesophilic bacteria, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans; chemical contaminants such as lead, cadmium, arsenic, and mercury; and naturally occurring toxins, such as allergens. The toxicological assessment considers both local effects (such as skin sensitisation, eye/skin irritation, and photo-induced effects) and systemic effects (including acute dermal toxicity, sub-acute and sub-chronic toxicity, mutagenicity and carcinogenicity, reproductive toxicity, and toxicokinetics). The EU legislative requirements prohibit the use of animal-based tests for the toxicological evaluation of cosmetic ingredients, paving the way for alternatives termed as New Approach Methodologies (NAMs). The validation of NAMs is critical for their wider usage, and despite advancements, few have been validated, particularly for systemic toxicity testing. The use of NAMs in evaluating the safety of complex natural cosmetic ingredients is further examined.