Neurodegenerative diseases like amyotrophic lateral sclerosis are often associated with mutations in proteins which can form stress granules by liquid-liquid phase separation (LLPS). Formation of these condensate phases requires a complex molecular grammar for protein-protein interactions which, when aberrant, can lead to altered condensation and disease phenotypes. We asked whether condensation of ALS-associated proteins could be a drug target. Screening identified lipoamide, a small molecule which specifically reduces cytoplasmic condensation (stress granules) of FUS and other ALS-associated proteins. In vitro, lipoamide partitions into and alters the physical properties of condensates made by FUS, similarly in cells lipoamide partitions into stress granules. Thermal proteome profiling showed lipoamide stabilises proteins with R/Y-rich intrinsically disordered domains in cells, including SRSF1 and SFPQ, two stress granule proteins which are necessary for lipoamide activity. In animals, lipoamide reduces aging-associated aggregation of a stress granule protein and improves neuronal morphology and recovers motor defects caused by ALS-associated FUS and TDP43 mutations. Lipoamide is a well-tolerated specific small molecule modulator of stress granule condensation with drug-like potential.