Officers made the traffic stop on Highway 55 near Debden, Sask., at around 5 p.m. CT on April 21.
RCMP said they seized prescription pills and what is believed to be crystal meth.
Police conducted a follow-up search at a home on Big River First Nation where they seized weapons, including an imitation firearm.
Leslie Keenatch, 43, and Sandra Keenatch, 34, both from Big River First Nation, are facing numerous charges and are scheduled to appear in court on June 12.
Debden is approximately 170 kilometres north of Saskatoon.