Alzheimer’s disease (AD) is a progressive neurodegenerative condition that is defined by cognitive impairment, amyloid-beta (Aβ) plaque deposition, and hyperphosphorylated tau aggregates. While rodent models have played a crucial role in the investigation of AD pathogenesis, small animal models like zebrafish (Danio rerio) and the nematode Caenorhabditis elegans provide unique benefits for the exploration of disease mechanisms and the acceleration of preclinical research. Zebrafish, with their vertebrate neuroanatomy and human genetic homology, provide the opportunity to investigate learning, memory, and complex behavior in an affordable, high-throughput environment. Zebrafish models of disease recapitulate a number of pathological features of AD and allow real-time observation of disease progression, yielding insights into Aβ and tau toxicity. Parallel to this, C. elegans is a powerful system for rapid pharmaceutical and genetic screening since it possesses short lifespan, accurate nervous system with 302 neurons, and amenability to RNAi and CRISPR/Cas9 tools. Transgenic Caenorhabditis elegans lines expressing proteins linked with AD display crucial mechanisms that control proteostasis, neuronal damage, and aging. Both zebrafish and C. elegans cover important gaps left by different rodent models and offer complementary systems for dissecting AD pathology, setting drug targets, and speeding translational pipelines.