Motor and non-motor manifestations are common and disabling features of hereditary spastic paraplegia (HSP). Botulinum toxin type A (Btx-A) is considered effective for spasticity and may improve gait in these patients. Little is known about the effects of Btx-A on non-motor symptoms in HSP patients. Objective To assess the efficacy of Btx-A on motor and non-motor manifestations in HSP patients. Methods Thirty-three adult patients with a clinical and molecular diagnosis of HSP were evaluated before and after Btx-A injections. Results Mean age was 41.7 ± 13.6 years and there were 18 women. Most patients had a pure phenotype and SPG4 was the most frequent genotype. The Btx-A injections resulted in a decrease in spasticity at the adductor muscles, and no other motor measure was significantly modified. In contrast, fatigue scores were significantly reduced after Btx-A injections. Conclusion Btx-A injections resulted in no significant functional motor improvement for HSP, but fatigue improved after treatment.