Neurotoxins of natural origin wield formidable potential, showcasing a diverse array of compounds derived from plants, animals, and microorganisms that possess the ability to perturb normal neural function. This book chapter endeavors to explore the wide spectrum of neurotoxins found in nature, elucidating their intricate mechanisms of action and consequential effects on the nervous system. The chapter begins by offering an overview of neurotoxins’ classification based on their sources, encompassing venoms, poisons, and other biological materials. It delves into the multifaceted chemical structures and intricate pathways through which these toxins exert their influence, disrupting neurotransmission, ion channels, and synaptic processes. Special emphasis is placed on their diverse physiological effects, including paralysis, convulsions, and neuromuscular blockade, highlighting the critical role these toxins play in predator–prey interactions, defense mechanisms, and pharmaceutical research. Furthermore, this chapter explores case studies of prominent neurotoxins, such as botulinum toxin, tetanus toxin, tetrodotoxin, and α-latrotoxin, elucidating their specific mechanisms of action and potential therapeutic applications. The evolving landscape of research into harnessing these toxins for medicinal purposes and drug development is also discussed, shedding light on their promising roles in neurology, pain management, and neuromodulation therapies. The comprehensive analysis of neurotoxins of natural origin provided in this chapter not only underscores their profound impact on the nervous system but also highlights their potential as valuable tools in understanding neural pathways and developing novel therapeutic interventions.