Invertebrate animal studies of methamphetamine (METH) could allow for high throughput, inexpensive, and high-animal number pharmacology and toxicology studies. We hypothesized that in Periplaneta americana cockroaches, METH would increase locomotion compared to saline and produce lethality. Lethal dose, 50% (LD₅₀) was determined with 0–1,780 µg/g (mg/kg) METH (n = 15–16/group) using logit analysis. Locomotor activity after METH (0–560 mg/kg, intra-abdominal, n = 8 per group) administration and spontaneous locomotor activity in surviving cockroaches in an open field 24 h after LD₅₀ study doses was measured with Noldus Ethovision. The LD₅₀ of METH was 823.1 mg/kg (more than 10-fold greater than the value in rats). There were significant decreases in spontaneous locomotor activity in surviving cockroaches after administration of 650 and 750 mg/kg METH (P < 0.05). While 100 mg/kg METH did not significantly increase METH locomotor activity relative to saline, 300 mg/kg METH significantly increased locomotor activity compared to saline (P < 0.05), and 560 mg/kg METH resulted in most of the cockroaches slowly moving around the open field in the supine position for most of the trial. In conclusion, METH produces pharmacological and toxicological effects in P. americana. The high availability, low cost, and relative ease of use of these animals makes them a potential, very accessible option for studying METH use disorder.