The gum, which has seen sales grow 30% month-on-month since launching into coffee shops and independent stores in January, hits Waitrose shelves later this month with an rsp of £1.35.
The deal would "massively" boost sales and demand, predicted Peppersmith, founded by two former Innocent colleagues this January.
Waitrose said that it was attracted by Peppersmith's claims that it was the only gum that used British-sourced peppermint and the only one other than Wrigley Orbit accredited by the British Dental Health Foundation to use a natural sweetener.
"We are always looking for innovative British products and Peppersmith gum is a great example of this," said confectionery buyer Louise O'Brien.
"We know Waitrose customers appreciate sustainably sourced products and I'm sure they'll be intrigued by this natural gum that uses a quality British ingredient Black Mitcham peppermint."
The deal comes as Peppersmith launches into Holland and Belgium after winning the Monoprix Trends & Innovations Prize at Sial last month.
Co-founder Mike Stevens said the company was growing so quickly it had been forced to look for a head of business development. "We had always planned to work with a big customer like Waitrose but we haven't achieved everything we set out to achieve just yet," said Stevens.
New products would be launched next year, he added.