The social network is reaching out to people affected, saying they have until December 11 to log onto the service in order to prevent the removal.
While the move will be celebrated by those looking for much-desired handle names that lay dormant, some have expressed concern about losing accounts which belonged to someone who has died.
Without knowing their password, loved ones stand to lose memories on the platform once a person has died, though Twitter said it is thinking about ways it could memorialise these accounts.
Twitter’s biggest rival, Facebook, allows family and friends of the deceased to freeze their account, so it can still be viewed and messages can be posted on their page.
There is no indication of how soon freed-up account names will be made available for others once the cull gets under way.
According to emails received by inactive account holders obtained by the BBC, the Twitter clean-up is about ensuring users agree to their updated terms and privacy policies.
“As part of our commitment to serve the public conversation, we’re working to clean up inactive accounts to present more accurate, credible information people can trust across Twitter,” a spokesman for the social media platform said.
“Part of this effort is encouraging people to actively log in and use Twitter when they register an account, as stated in our Inactive Accounts Policy.
“We have begun proactive outreach to many accounts who have not logged into Twitter in over six months to inform them that their accounts may be permanently removed due to prolonged inactivity.”
People are not required to tweet from their account to keep it active, they just need to sign in and follow on-screen prompts.