Some 130 people have reportedly been shot dead by Bangladeshi security forces since May 15 and another 15,000 arrested in the Philippines-style crackdown aimed to halt the spread of methamphetamine and other illegal drugs.
"I am gravely concerned that such a large number of people have been killed," UN High Commissioner for Human Rights Zeid Ra'ad Al Hussein said in a statement.
He also voiced concern about government reaction, which "has been to assure the public that none of these individuals were 'innocent'.
"Such statements are dangerous and indicative of a total disregard for the rule of law," he said.
"People do not lose their human rights because they use or sell drugs."
Bangladesh has been struggling to contain a surging drug trade.
Police have vowed to stamp out "yaba", a very popular street pill made of caffeine and methamphetamine.
Authorities last year seized a record 40 million yaba tablets, but said an estimated 250-300 million others entered the market, due in part to large quantities coming across the border from major producer Myanmar.
Nine million yaba tablets were seized in less than three months earlier this year, including nearly two million in a single haul.
The rights commissioner stressed that "the presumption of innocence and the right to due process must be at the forefront of any efforts to tackle crime."
"Given the large number of people arrested, there is a high likelihood that many people may have been arbitrarily detained, without due regard for their rights."
Urging Bangladesh to investigate reports of extra-judicial killings and hold the perpetrators to account, he also voiced concern that already vulnerable slum communities were particular targets and that the crackdown appeared to be hampering drug users from accessing health services.
The alleged dealers killed in Bangladesh mainly died in what authorities described as shootouts, but parallels have been drawn to the Philippines where police have been accused of executing suspects.
"There is no doubt that the trafficking and sale of illegal narcotics leads to tremendous suffering," the rights chief added.
"But extra-judicial killings, arbitrary arrests and the stigmatisation of people who use drugs cannot be the answer."
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